Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

File： Kurabe(iScience,2022).pdf

DOI： 10.1016/j.isci.2022.105555

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

File： Matsuda(J Pain,2022).pdf

DOI： 10.1016/j.jpain.2022.06.001

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

BACKGROUND: Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have been conducted to assess this. This randomized, double-blinded, placebo-controlled trial aimed to test the hypothesis that low-dose droperidol reduced TCE-MEP amplitudes. METHODS: Twenty female patients with adolescent idiopathic scoliosis, aged between 12 and 20 years, and scheduled to undergo corrective surgery were randomly allocated to receive droperidol (20 µg/kg) or 0.9% saline. After recording baseline TCE-MEPs, the test drug was administered, following which TCE-MEP recordings were carried out every 2 minutes for up to 10 minutes. The primary outcome was the minimum relative TCE-MEP amplitude (peak-to-peak amplitude, percentage of baseline value) recorded in the left tibialis anterior muscle. Secondary outcomes included minimum relative MEP amplitudes recorded from all other muscle groups monitored in the study. Data are expressed as medians (interquartile range). RESULTS: The TCE-MEP amplitude of the left tibialis anterior muscle was significantly reduced following droperidol administration compared with saline (37% [30% to 55%] vs. 76% [58% to 93%], respectively, P<0.01). In the other muscles, the amplitudes were reduced in the droperidol group, except for the bilateral abductor pollicis brevis and the left quadriceps femoris muscles. The relative amplitude of the bilateral F waves recorded from the gastrocnemius was decreased in the droperidol group. CONCLUSIONS: Low-dose droperidol (20 µg/kg) reduced TCE-MEP amplitudes. Anesthesiologists should pay attention to the timing of droperidol administration during intraoperative TCE-MEP recordings, even if used in a low dose.

File： Mitsuma(J Neurosurg Anesth,2021).pdf

DOI： 10.1097/ANA.0000000000000784

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File： Ohashi(Pain,2022).pdf

DOI： 10.1097/j.pain.0000000000002523

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File： Kita(Medicine,2022).pdf

DOI： 10.1097/md.0000000000029709

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File： Ohashi(Neurocience,2022).pdf

DOI： 10.1016/j.neuroscience.2022.03.023

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

Yokukansan (YKS) is a traditional Japanese herbal (Kampo) medicine prescribed for anxiety. In this randomized controlled trial, we compared the subjective assessment of anxiety using questionnaires and its objective assessment using salivary alpha-amylase concentrations in YKS and control (CNT) groups of women undergoing breast surgery. The trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000028998), and the investigators were blinded to drug administration. One hundred patients who underwent breast cancer surgery were allocated to either the YKS or the CNT group. Finally, 35 and 42 patients in the YKS and CNT groups were analyzed, respectively. The YKS group received two 2.5 g doses of the medication before sleeping on the night before surgery and 2 h before inducing anesthesia, while the CNT group did not receive medication preoperatively. Patients answered two questionnaires, the Hospital Anxiety and Depression Scale and the State-Trait Anxiety Inventory, pre-and postoperatively as subjective anxiety assessments. As an objective anxiety indicator, salivary alpha-amylase levels were measured the day before, directly before, and the day after surgery (T3). In the YKS group, salivary alpha-amylase scores directly before operation were significantly lower than those on the day before surgery and at one day postoperatively (F [2,150] = 3.76, p = 0.03). Moreover, the Hospital Anxiety and Depression Scale-Anxiety and State-Trait Anxiety Inventory-Trait scores were significantly more improved postoperatively in the YKS group than in the CNT group (difference in Hospital Anxiety and Depression Scale-Anxiety: YKS, mean -2.77, 95% confidence interval [-1.48 –-4.06], p &lt;0.001, and CNT, -1.43 [-0.25–-2.61], p = 0.011; and difference in State-Trait Anxiety Inventory: YKS group, -4.23 [-6.95–-1.51], p = 0.0004; and CNT group, 0.12 [-2.36–2.60], p = 0.92). No side effects were associated with YKS. YKS may reduce perioperative anxiety in patients undergoing surface surgery.

File： Tanaka M(PlosOne,2021).pdf

DOI： 10.1371/journal.pone.0260524

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BACKGROUND: An epidurally administered local anesthetic acts primarily on the epidural nerve roots and can act directly on the spinal cord through the dural sleeve. We hypothesized that epidurally administered ropivacaine would reduce the amplitude of transcranial electrical motor-evoked potentials by blocking nerve conduction in the spinal cord. Therefore, we conducted a double-blind, randomized, controlled trial. METHODS: Thirty adult patients who underwent lung surgery were randomly allocated to 1 of 3 groups, based on the ropivacaine concentration: the 0.2% group, the 0.375% group, and the 0.75% group. The attending anesthesiologists, neurophysiologists, and patients were blinded to the allocation. The epidural catheter was inserted at the T5-6 or T6-7 interspace by a paramedian approach, using the loss of resistance technique with normal saline. General anesthesia was induced and maintained using propofol and remifentanil. Transcranial electrical motor-evoked potentials were elicited by a train of 5 pulses with an interstimulus interval of 2 milliseconds by using a constant-voltage stimulator and were recorded from the tibialis anterior muscle. Somatosensory-evoked potentials (SSEPs) were evoked by electrical tibial nerve stimulation at the popliteal fossa. After measuring the baseline values of these evoked potentials, 10 mL of epidural ropivacaine was administered at the 0.2%, 0.375%, or 0.75% concentration. The baseline amplitudes and latencies recorded before administering ropivacaine were defined as 100%. Our primary end point was the relative amplitude of the motor-evoked potentials at 60 minutes after the epidural administration of ropivacaine. We analyzed the amplitudes and latencies of these evoked potentials by using the Kruskal-Wallis test and used the Dunn multiple comparison test as the post hoc test for statistical analysis. RESULTS: The data are expressed as the median (interquartile range). Sixty minutes after epidurally administering ropivacaine, the motor-evoked potential amplitude was lower in the 0.75% group (7% [3%-18%], between-group difference P < .001) and in the 0.375% group (52% [43%-59%]) compared to that in the 0.2% group (96% [89%-105%]). The latency of SSEP was longer in the 0.75% group compared to that in the 0.2% group, but the amplitude was unaffected. CONCLUSIONS: Epidurally administered high-dose ropivacaine lowered the amplitude of motor-evoked potentials and prolonged the onset latencies of motor-evoked potentials and SSEPs compared to those in the low-dose group. High-dose ropivacaine can act on the motor pathway through the dura mater.

File： Furutani(A&A,2021).pdf

DOI： 10.1213/ane.0000000000005236

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BACKGROUND: A low-dose bolus or infusion of ketamine does not affect transcranial electrical motor-evoked potential (MEP) amplitude, but a dose ≥1 mg/kg may reduce MEP amplitude. We conducted a randomized, double-blinded, placebo-controlled study to evaluate the effect of ketamine (1 mg/kg) on transcranial electrical MEP. METHODS: Twenty female patients (aged 12 to 18 y) with adolescent idiopathic scoliosis scheduled to undergo posterior spinal fusion were randomly allocated to receive ketamine or saline. General anesthesia was induced and maintained with continuous infusions of propofol and remifentanil. MEP was elicited by supramaximal transcranial electrical stimulation. MEP recordings were obtained at baseline and then at 2, 4, 6, 8, and 10 minutes after administration of ketamine (1 mg/kg) or saline (0.1 ml/kg). The primary endpoint was the minimum relative MEP amplitude (peak-to-peak amplitude, % of baseline value) recorded from the left tibialis anterior muscle. The baseline amplitude recorded before test drug administration was defined as 100%. RESULTS: Medians (interquartile range) minimum MEP amplitudes in the left tibialis anterior muscle in the ketamine and saline groups were 26% (9% to 34%) and 87% (55% to 103%) of the baseline value, respectively (P<0.001). MEP amplitudes in other muscles were significantly reduced by ketamine. The suppressive effect of ketamine lasted for at least 10 minutes in each muscle. CONCLUSION: A 1-mg/kg bolus dose of ketamine can reduce MEP amplitude. Anesthesiologists should consider the dosage and timing of intravenous ketamine administration during MEP monitoring.

File： Furutani (2019).pdf

DOI： 10.1097/ANA.0000000000000653

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Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：克誠堂出版(株)  

成人ムコ多糖症II型患者では、周術期の気道・呼吸管理が問題になる。本症例は意識下、気管支鏡ガイド下に経口挿管を試みたが、ムコ多糖の蓄積による気道のねじれと狭窄のため困難であった。経鼻アプローチに変更すると、咽頭軸との角度が緩やかになり比較的容易に挿管できた。成人症例では経鼻挿管が有用である可能性が示唆された。(著者抄録)

File： 成人ムコ多糖症（三ッ間,2021,麻酔）.pdf

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01397&link_issn=&doc_id=20210601120006&doc_link_id=%2Fad3msuie%2F2021%2F007006%2F007%2F0602b0605%26dl%3D3&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fad3msuie%2F2021%2F007006%2F007%2F0602b0605%26dl%3D3&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_4.gif

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

PURPOSE: Propofol inhibits the amplitudes of transcranial electrical motor-evoked potentials (TCE-MEP) in a dose-dependent manner. However, the mechanisms of this effect remain unknown. Hence, we investigated the spinal mechanisms of the inhibitory effect of propofol on TCE-MEP amplitudes by evaluating evoked electromyograms (H-reflex and F-wave) under general anesthesia. METHODS: We conducted a prospective, single-arm, interventional study including 15 patients scheduled for spine surgery under general anesthesia. Evoked electromyograms of the soleus muscle and TCE-MEPs were measured at three propofol concentrations using target-controlled infusion (TCI: 2.0, 3.0, and 4.0 µg/mL). The primary outcome measure was the left H-reflex amplitude during TCI of 4.0- compared to 2.0-µg/mL propofol administration. RESULTS: The median [interquartile range] amplitudes of the left H-reflex were 4.71 [3.42-6.60] and 5.6 [4.17-7.46] in the 4.0- and 2.0-μg/mL TCI groups (p = 0.4, Friedman test), respectively. There were no significant differences in the amplitudes of the right H-reflex and the bilateral F-wave among these groups. However, the TCE-MEP amplitudes significantly decreased with increased propofol concentrations (p < 0.001, Friedman test). CONCLUSION: Propofol did not affect the amplitudes of the H-reflex and the F-wave, whereas TCE-MEP amplitudes were reduced at higher propofol concentrations. These results suggested that propofol can suppress the TCE-MEP amplitude by inhibiting the supraspinal motor pathways more strongly than the excitability of the motor neurons in the spinal cord.

File： Deguchi2021_Article_PropofolReducesTheAmplitudeOfT.pdf

DOI： 10.1007/s00540-021-02927-7

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File： Deguchi(J Clin MonitComput.2021).pdf

DOI： 10.1007/s10877-020-00464-4

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File： 相馬先生（JA Clinical Reports).pdf

DOI： 10.1186/s40981-020-00349-0

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File： Quadratus lumborum block(Watanabe,2020,JA CR).pdf

DOI： 10.1186/s40981-020-00342-7

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Other Link： http://link.springer.com/article/10.1186/s40981-020-00342-7/fulltext.html

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BACKGROUND: Nasogastric tubes can be easily inserted in patients under general anesthesia. However, for difficult cases, insertion techniques that can be used in routine clinical practice are limited. SUZY forceps are designed for the removal of pharyngolaryngeal foreign bodies under guidance of a McGrath videolaryngoscope. We hypothesized that using SUZY forceps under McGrath videolaryngoscopic guidance may facilitate nasogastric tube insertion and tested this in a randomized controlled trial. METHODS: Adult patients who underwent gastrointestinal or hepato-pancreato-biliary surgery were randomly allocated to 2 groups; the SUZY group and the Magill group. Patients, nurses, and all clinical staff except for the attending anesthesiologist were blinded to group assignment throughout the study. After anesthesia induction, insertion of the nasogastric tube was performed by skilled anesthesiologists with either SUZY or Magill forceps according to group allocation under McGrath videolaryngoscopic guidance. The primary endpoint was insertion time which was defined as the time required to advance the nasogastric tube by 55 cm from the nostril. Secondary endpoints were the success rates of the nasogastric tube insertion, which were defined as a 55-cm advancement from the nostril at the 1st, 2nd, and 3rd attempt, proper insertion rate, the severity of pharyngolaryngeal complications, and hemodynamic parameters during nasogastric tube insertion. RESULTS: Sixty patients were randomized and none of these patients were excluded from the final analysis. The median [interquartile range] insertion time was 25 [18-33] seconds in the SUZY group, and 33 [21-54] seconds in the Magill group (P = .02). Success rates were not different between the groups (97% and 80% in the SUZY and Magill group at 1st attempt, respectively, P = .10). Both, the severity score of the mucosal injury and the severity of sore throat were higher in the Magill than in the SUZY group, whereas the degree of hoarseness did not differ between the 2 groups. Hemodynamic parameters were not significantly different between the groups. CONCLUSION: Using SUZY forceps under McGrath videolaryngoscopic guidance reduced the time required to insert a nasogastric tube and the severity of pharyngolaryngeal complications, when compared to using Magill forceps.

File： Furutani(2020,Medicine).pdf

DOI： 10.1097/md.0000000000022545

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

File： 番場景子・学位論文.pdf

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File： Imai(JA,2020).pdf

DOI： 10.1007/s00540-020-02807-6

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

This case report describes a neonate with tracheal aplasia first diagnosed after birth due to the presentation of respiratory distress, absence of crying, and unsuccessful tracheal intubation. The most common finding with tracheal aplasia is polyhydramnios. However, diagnosis remains challenging in the prenatal period. In this case, maternal obesity and gestational diabetes made diagnosis more difficult. The only lifesaving treatment available is ventilation through esophageal intubation or tracheostomy. However, in some cases, tracheostomy is not an option.

File： Congenital Tracheal(Yamamoto,A&A,2020).pdf

DOI： 10.1213/xaa.0000000000001200

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File： 9年間肘痛のみの症状が持続した尺骨神経炎の1例.pdf

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Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

File： 難治性の直腸がん術後の肛門痛に漢方治療が奏効した一症例.pdf

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Language：English   Publishing type：Doctoral thesis  

KEY POINTS: Neuropathic pain spreads spatially beyond the injured sites, and the mechanism underlying the spread has been attributed to inflammation occurring in the spinal cord. However, the spatial spread of spinal/cortical potentiation induced by conduction block of the peripheral nerves can be observed prior to inflammation. In the present study, we found that spreading potentiation and hypersensitivity acutely induced by unilateral hindpaw ischaemia are nitric oxide (NO)-dependent and that NO is produced by ischaemia and quickly diffuses within the spinal cord. We also found that NO production induced by ischaemia is not observed in the presence of an antagonist for group II metabotropic glutamate receptors (mGluRs) and that neuronal NO synthase-positive dorsal horn neurons express group II mGluRs. These results suggest strongly that NO-mediated spreading potentiation in the spinal cord is one of the trigger mechanisms for neuropathic pain. ABSTRACT: Cortical/spinal responses to hindpaw stimulation are bilaterally potentiated by unilateral hindpaw ischaemia in mice. We tested the hypothesis that hindpaw ischaemia produces nitric oxide (NO), which diffuses in the spinal cord to induce spatially spreading potentiation. Using flavoprotein fluorescence imaging, we confirmed that the spreading potentiation in hindpaw responses was induced during ischaemia in the non-stimulated hindpaw. This spreading potentiation was blocked by spinal application of l-NAME, an inhibitor of NO synthase (NOS). Furthermore, no spreading potentiation was observed in neural NOS (nNOS) knockout mice. Spinal application of an NO donor was enough to induce cortical potentiation and mechanical hypersensitivity. The spatial distribution of NO during unilateral hindpaw ischaemia was visualized using 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM). An increase in fluorescence derived from the complex of DAF-FM with NO was observed on the ischaemic side of the spinal cord. A similar but smaller increase was also observed on the contralateral side. Somatosensory potentiation after hindpaw ischaemia is known to be inhibited by spinal application of LY354740, an agonist of group II metabotropic glutamate receptors (mGluRs). We confirmed that the spinal DAF-FM fluorescence increases during hindpaw ischaemia were not observed in the presence of LY354740. We also confirmed that approximately half of the nNOS-positive neurons in the superficial laminae of the dorsal horn expressed mGluR2 mRNA. These results suggest that disinhibition of mGluR2 produces NO which in turn induces a spreading potentiation in a wide area of the spinal cord. Such spreading, along with the consequent non-specific potentiation in the spinal cord, may trigger neuropathic pain.

File： Onishi(JP,2019).pdf

DOI： 10.1113/JP277615

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Language：English   Publishing type：Doctoral thesis   Publisher：Elsevier BV  

File： Seino(2019,J of Cardiothoracic and Vascular Anesthesia).pdf

DOI： 10.1053/j.jvca.2018.10.023

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：真興交易(株)医書出版部  

非常に稀な自然気管破裂の1症例を経験した。症例は85歳の女性で、高度肥満、閉塞性睡眠時無呼吸症候群、関節リウマチの現病歴があり、ステロイド治療中であった。外傷などの誘因なく背部痛、呼吸困難が出現し、気管支鏡で分岐部直上の気管破裂を認めた。手術のために挿管された二腔チューブが、気管裂傷部に迷入し、換気困難になった。体外式膜型人工肺を使用して、手術を完遂し、治療を継続したが死亡した。(著者抄録)

File： 清水（臨床麻酔,2019）.pdf

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Language：English   Publishing type：Doctoral thesis  

BACKGROUND: The neurosteroid dehydroepiandrosterone sulphate (DHEAS) activates the sigma-1 receptor, inhibits gamma-aminobutyric acid A (GABAA) and glycine receptors, and induces hyperalgesic effects. Although its effects have been studied in various tissues of the nervous system, its synaptic mechanisms in nociceptive pathways remain to be elucidated. METHODS: The threshold of mechanical hypersensitivity and spontaneous pain behaviour was assessed using the von Frey test in adult male Wistar rats after intrathecal administration of DHEAS. We also investigated the effects of DHEAS on synaptic transmission in the spinal dorsal horn using slice patch-clamp electrophysiology. RESULTS: Intrathecally administered DHEAS elicited dose-dependent mechanical hyperalgesia and spontaneous pain behaviours (withdrawal threshold: saline; 51.0 [20.1] g, 3 μg DHEAS; 14.0 [7.8] g, P<0.01, 10 μg DHEAS; 6.9 [5.2] g, 15 min after administration, P<0.001). DHEAS at 100 μM increased the frequency of miniature postsynaptic currents in the rat dorsal spinal horn; this increase was extracellular Ca2+-dependent but not sigma-1 and N-methyl-d-aspartate receptor-dependent. DHEAS suppressed the frequency of miniature inhibitory postsynaptic currents in a GABAA receptor- and sigma-1 receptor-dependent manner. CONCLUSIONS: These results suggest that DHEAS participates in the pathophysiology of nociceptive synaptic transmission in the spinal cord by potentiation of glutamate release and inhibition of the GABAA receptor.

File： Yamamoto G(BJA,2019).pdf

DOI： 10.1016/j.bja.2019.03.026

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Noradrenaline (NA) modulates the spinal motor networks for locomotion and facilitates neuroplasticity, possibly assisting neuronal network activation and neuroplasticity in the recovery phase of spinal cord injuries. However, neither the effects nor the mechanisms of NA on synaptic transmission and neuronal excitability in spinal ventral horn (VH) neurons are well characterized, especially in rats aged 7 postnatal days or older. To gain insight into NA regulation of VH neuronal activity, we used a whole-cell patch-clamp approach in late neonatal rats (postnatal day 7-15). In voltage-clamp recordings at -70 mV, NA increased the frequency and amplitude of excitatory postsynaptic currents via the activation of somatic α1- and β-adrenoceptors of presynaptic neurons. Moreover, NA induced an inward current through the activation of postsynapticα1- and β-adrenoceptors. At a holding potential of 0 mV, NA also increased frequency and amplitude of both GABAergic and glycinergic inhibitory postsynaptic currents via the activation of somatic adrenoceptors in presynaptic neurons. In current-clamp recordings, NA depolarized resting membrane potentials and increased the firing frequency of action potentials in VH neurons, indicating that it enhances the excitability of these neurons. Our findings provide new insights that establish NA-based pharmacological therapy as an effective method to activate neuronal networks of the spinal VH in the recovery phase of spinal cord injuries.

File： Neuroscience 論文.pdf

DOI： 10.1016/j.neuroscience.2019.03.026

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Lamina X is localized in the spinal cord within the region surrounding the central canal and receives descending projections from the supraspinal nuclei. Norepinephrine (NE) is a neurotransmitter in descending pathways emanating from the brain stem; NE-containing fibers terminate in the spinal dorsal cord, particularly in the substantia gelatinosa (SG). NE enhances inhibitory synaptic transmission in SG neurons by activating presynaptic α1-receptors and hyperpolarizes the membranes of SG neurons by acting on α2-receptors; NE may thus act directly on SG neurons of the dorsal spinal cord and inhibit nociceptive transmission at the spinal level. NE-containing fibers also reportedly terminate in lamina X, suggesting that NE also modulates synaptic transmission in lamina X. However, the cellular mechanisms underlying such action have not been investigated. We hypothesized that NE might directly act on lamina X and enhance inhibitory synaptic transmission therein. Using rat spinal cord slices and in vitro whole-cell patch-clamps, we found that the bath-application of NE to lamina X does not affect the excitatory interneurons but enhances GABAergic and glycinergic miniature inhibitory postsynaptic currents (mIPSCs) and induces an outward current. NE-induced enhancement of mIPSCs was blocked by α1A-receptor antagonists, and NE-induced outward current was blocked by α2-receptor antagonists. NE did not affect GABA- or glycine- induced outward currents. These findings are similar to those obtained from SG neurons: NE may act at presynaptic terminals of GABAergic and glycinergic interneurons on lamina X to facilitate inhibitory-transmitter release through α1A-receptor activation and directly induce inhibitory interneuron membrane hyperpolarization through α2-receptors activation.

File： Ohashi(Neurocience,2019).pdf

DOI： 10.1016/j.neuroscience.2019.04.004

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BACKGROUND: Radiation enteritis following radiotherapy targeting the abdomen occasionally causes ulcers or ileus, which can be difficult to treat and usually progressive and refractory, significantly degrading the patient's quality of life. CASE PRESENTATION: A 58-year-old woman had undergone surgery for cervical cancer approximately 21 years ago. During treatment, she had also received radiotherapy targeting the pelvis and stomach. She presented with complaints of vomiting and lower abdominal pain and was subsequently diagnosed with multiple gastric ulcers, enterocolitis, and paralytic ileus due to late radiation-induced sequelae. We reasoned that visceral sympathetic block would improve the abdominal symptoms; therefore, we performed a splanchnic nerve block and an inferior mesenteric artery plexus block. As predicted, these block procedures improved the symptoms. CONCLUSIONS: Radiation enteritis is an iatrogenic disease, and there is no established treatment for intractable cases. However, visceral sympathetic nerve block may show efficacy as a potential therapy for radiation enteritis-associated abdominal pain and ileus.

File： Neural block therapy for radiation enteritis(Tanaka,JACR,2019).pdf

DOI： 10.1186/s40981-019-0239-9

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Termedia Sp. z.o.o.  

File： Yamamoto(Anaesthesiology Intensive Therapy,2019.pdf

DOI： 10.5114/ait.2019.89225

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Opioid-related postoperative nausea and vomiting should not occur following remifentanil administration because of its relatively short time to elimination. However, studies have indicated that the incidence of postoperative nausea and vomiting associated with remifentanil is similar to that with other opioids. Hence, we aimed to determine whether intraoperative remifentanil itself is associated with postoperative nausea and vomiting when postoperative pain is managed without opioid use. In this prospective pilot study, 150 patients who underwent unilateral upper limb surgery under general anesthesia with brachial plexus block were included. Patients in the remifentanil and control groups received 0.5 µg/kg/min remifentanil and saline, respectively. Postoperative pain was managed using a brachial plexus block, non-steroidal anti-inflammatory drugs, and acetaminophen. The presence of postoperative nausea and vomiting within the first 24 h after anesthesia was assessed by an evaluator blinded to patient allocation. Eight patients were excluded from the final analysis, resulting in 72 and 70 patients in the remifentanil and control groups, respectively. Postoperative nausea and vomiting within 24 h after surgery occurred in 11 and 9 patients in the remifentanil and control groups, respectively. These data suggest that remifentanil use only minimally affects the incidence of postoperative nausea and vomiting under sevoflurane anesthesia. UMIN Clinical Trials Registry identification number: UMIN000016110.

File： Watanabe T(JA,2018).pdf

DOI： 10.1007/s00540-018-2550-4

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OBJECTIVES: Determination of the appropriate tracheal tube size using formulas based on age or height often is inaccurate in pediatric patients with congenital heart disease (CHD), particularly in those with high pulmonary arterial pressure (PAP). Here, the authors compared tracheal diameters between pediatric patients with CHD with high PAP and low PAP. DESIGN: Retrospective clinical study. SETTING: Hospital. PARTICIPANTS: Pediatric patients, from birth to 6 months of age, requiring general anesthesia and tracheal intubation who underwent computed tomography were included. Patients with mean pulmonary artery pressure >25 mmHg were allocated to the high PAP group, and the remaining patients were allocated to the low PAP group. The primary outcome was the tracheal diameter at the cricoid cartilage level, and the secondary goal was to observe whether the size of the tracheal tube was appropriate compared with that obtained using predictable formulas based on age or height. MEASUREMENTS AND MAIN RESULTS: The mean tracheal diameter was significantly larger in the high PAP group than in the low PAP group (p < 0.01). Pediatric patients with high PAP required a larger tracheal tube size than predicted by formulas based on age or height (p = 0.04 for age and height). CONCLUSIONS: Pediatric patients with high PAP had larger tracheal diameters than those with low PAP and required larger tracheal tubes compared with the size predicted using formulas based on age or height.

File： Ohashi N (J Car and Vasc Anes,2018).pdf

DOI： 10.1053/j.jvca.2017.12.004

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BACKGROUND: It is believed that ketamine does not affect motor-evoked potential amplitude, whereas various anesthetic drugs attenuate the amplitude of transcranial motor-evoked potential. However, we encountered a patient with marked attenuation of motor-evoked potential amplitude after intravenous bolus administration of ketamine. CASE PRESENTATION: A 15-year-old Japanese girl with a diagnosis of adolescent idiopathic scoliosis was admitted to our hospital to undergo posterior spinal fusion at T4-L3. After induction of general anesthesia using a continuous infusion of propofol and remifentanil, we confirmed that transcranial electrical motor-evoked potentials were being recorded correctly. Ketamine 1.25 mg/kg was administered intravenously for intraoperative and postoperative analgesia. About 3 minutes later, the motor-evoked potential amplitude was markedly attenuated. No other drugs were administered except for ketamine. The patient's vital signs were stable, and the surgery had not yet started. The motor-evoked potential amplitude was recovered at about 6 minutes after administration of ketamine. The surgery was performed uneventfully, and the patient had no neurologic deficit when she emerged from general anesthesia. CONCLUSIONS: Although there is a widely held belief in the field of anesthesiology that ketamine does not affect motor-evoked potential amplitude, it has been suggested that ketamine could affect its monitoring.

File： Furutani(JM case reports,2018).pdf

DOI： 10.1186/s13256-018-1741-9

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We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as evidenced by lower concentrations of the free radical malonyldialdehyde in the spinal cord 3 h post-SCI. Malonyldialdehyde levels in the high-dose edaravone group were not reduced. Both moderate- and high-dose edaravone resulted in significant functional improvements, evidenced by better Basso-Beattie-Bresnahan (BBB) scores and better performance on an inclined plane during an 8 week period post-SCI. Both moderate- and high-dose edaravone significantly attenuated neuronal loss in the spinal cord at 8 weeks post-SCI, as evidenced by quantitative immunohistochemical analysis of NeuN-positive cells. In conclusion, early administration of a moderate dose of edaravone minimized the negative consequences of SCI and facilitated functional recovery.

File： Ishi (Brain Res, 2018).pdf

DOI： 10.1016/j.brainres.2017.12.035

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Background: Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand-foot syndrome (HFS) is the most common, occurring in 30%-50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. Materials and methods: To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. Results: A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow (p = 0.009) and significantly decreased occurrence of HFS (p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period (p = 0.035). Conclusion: The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow.

File： Kamimura K(Cancer management and research,2018).pdf

DOI： 10.2147/CMAR.S159370

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File： 大橋(Cardiovasular Anesthesia2018).pdf

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File： 原（麻酔, 2017）.pdf

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AIM
The kinetics of propofol are influenced by cardiac output. The aim of this study was to examine changes in blood propofol concentrations during phaeochromocytoma surgery using target-controlled infusion (TCI) anaesthesia with propofol.
METHODS
This is a prospective observational study. Ten patients with phaeochromocytoma who underwent unilateral adrenalectomy were included. Cardiac output was measured using an arterial pressure-based cardiac output analysis method. The target blood propofol concentrations were adjusted to maintain an approximate bispectral index (BIS) value of 40 before initiating surgery. The settings remained constant during surgery. Blood samples for propofol concentrations were collected from the radial artery at seven time points: two before tumour manipulation (T1, 2), two during tumour manipulation (T3, 4), and three after tumour vein ligation (T4-7). BIS values, the arterial pressure cardiac index (APCI) and haemodynamic parameters were measured at the same time points as the blood samples. The prop-ratio was calculated by dividing blood propofol concentrations by target concentrations of TCI.
RESULTS
APCI increased during tumour manipulation and after tumour vein ligation. The prop-ratio was reduced significantly by approximately 40% and showed a significant negative correlation with APCI. BIS values increased significantly and showed a significant negative correlation with the prop-ratio.
CONCLUSION
The increased APCI during tumour manipulation and after tumour vein ligation was associated with markedly reduced blood propofol concentrations. These results reveal that significant decreases in the anaesthetic effect may be observed in patients undergoing phaeochromocytoma surgery even if TCI anaesthesia is used with propofol.

File： Watanabe T(bjcp,2017).pdf

DOI： 10.1111/bcp.13334

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Background: Nasogastric tube (NGT) insertion is an easy procedure that can be routinely performed under general : anesthesia. However, for difficult cases, there are limited insertion techniques available in routine clinical practice, considering the flexibility of NGTs. The SUZY curved forceps are designed for the removal of pharyngolaryngeal foreign bodies under guidance of the McGRATH MAC (McG) videolaryngoscope. Because McG enables clear visualization of the esophageal inlet, we hypothesized that the SUZY forceps can facilitate easier NGT insertion compared with the conventional Magill forceps under McG guidance and designed a randomized, crossover manikin study to test this hypothesis.
Materials and Methods: Ten anesthesiologists participated in this study. Each participant was instructed to insert an NGT using either the SUZY or the Magill forceps under McG guidance. Both types of forceps were used by each participant in a computer-generated random order. The primary outcome measure was the number of "strokes" (1 stroke was defined by a specific sequence of participant actions) required to advance the NGT 30cm from the starting point. Data are expressed as medians (interquartile ranges [ranges]).
Results: The number of strokes required for NGT insertion was fewer in the SUZY group than in the Magill group {7 [7.0-12.5 (5-14)] vs 16.5 [13.5-20.3 (7-22)]; P &lt; .05}. The time required for NGT insertion was also lesser in the SUZY group than in the Magill group {15.4 [13.7-20.0 (7.0-38.3)] seconds vs 30.3 [22.0-42.3 (12.8-47.5) seconds]; P &lt; .05}.
Conclusions: The SUZY curved forceps facilitated NGT insertion more effectively than the Magill straight forceps under McG guidance. Our results suggest that NGT insertion using the SUZY forceps under McG guidance is a secure and easy procedure.

File： Furutani (Medicine,2018).pdf

DOI： 10.1097/MD.0000000000007983

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Persistent endoleaks may lead to adverse events after endovascular aortic repair. We prospectively examined the relationship between intraoperative residual spontaneous echocardiographic contrast (SEC) within the aneurysmal sac and the incidence of postoperative endoleaks in 60 patients undergoing thoracic endovascular aortic repair. Patients with SEC had a higher incidence of postoperative endoleaks than did patients without SEC within a few days postoperatively (60.0% vs 12.5%, respectively; P &lt; .001) and at 6 months postoperatively (40.0% vs 2.5%, respectively; P &lt; .001). Intraoperative confirmation of the absence of SEC may identify patients at low risk for persistent endoleaks after thoracic endovascular aortic repair.

File： Intraoperative_Detection_of_Persistent_Endolea.pdf

DOI： 10.1213/ANE.0000000000002207

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Abdominal radical trachelectomy has been identified as a surgical option for fertility preservation in cervical cancer patients, particularly in pregnant women who strongly desire to continue their pregnancy. Since this procedure requires operating in the uterus, the hardness of the uterus can affect the ease of surgery. Generally, sevoflurane is used for anesthesia in non-obstetric surgery for pregnant women because uterine relaxation is advantageous for uterine blood flow maintenance. However, the use of sevoflurane during radical trachelectomy has not been thoroughly evaluated. Here, we report on anesthesia use in three cases of abdominal radical trachelectomy during pregnancy. Propofol enabled maintenance of uterine tension while not significantly affecting fetal growth. It is important to consider maintenance of uterine tension and fetal circulation in anesthesia management. During the operation, we performed an ultrasound examination every 30 min to confirm fetal well-being. Although frequent fetal heart rate monitoring of the pre-viable fetus is not recommended, if fetal bradycardia is detected, sevoflurane may then be used to improve fetal circulation. Additionally, if the fetal heartbeat stops, a radical hysterectomy would then be required. Therefore, we consider that fetal heart rate monitoring during this procedure is necessary, and propofol is suitable as an anesthetic for this surgery during pregnancy.

File： Terukina(JA, 2017).pdf

DOI： 10.1007/s00540-017-2325-3

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File： 渡部(Eur J Anaesthesiology,2017).pdf

DOI： 10.1097/EJA.0000000000000572

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File： Petrenko(Anesthesiology,2017).pdf

DOI： 10.1097/ALN.0000000000001445

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Background: Postoperative pain management after upper limb surgery is important for preventing adverse events that can prolong hospital stay and cause readmission. This study aimed to identify the risk factors associated with rescue analgesic use on the first postoperative day after upper limb surgery performed under single-injection brachial plexus block (BPB). Findings: We retrospectively analyzed records from 930 patients who underwent upper limb surgery under a single-injection BPB. Postoperatively, patients were administered oral loxoprofen regularly and rescue analgesics when analgesia was insufficient. We assessed the association between patient, surgical information, and rescue analgesic use on the first day after surgery (from 7:00 PM on the day of surgery to 7:00 AM on the first postoperative day), using a logistic regression model. Multivariate analysis revealed a significant association between rescue analgesic use and bone surgery, in particular, osteotomy, ligament repair and reconstruction, osteosynthesis, treatment for an amputated digit, and surgical duration. Conclusion: Bone surgery (osteotomy, ligament repair and reconstruction, osteosynthesis, treatment for an amputated digit) and a longer operative time were risk factors for rescue analgesic use for treating postoperative pain after upper limb surgery performed under single-injection BPB.

File： Watanabe(JA Clinical aReport, 2017).pdf

DOI： 10.1186/s40981-017-0110-9

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File： 清水（臨床放射線,2017）.pdf

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Other Link： http://search.jamas.or.jp/link/ui/2017260615

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Background. The analgesic efficacy of continuous transversus abdominis plane (TAP) blocks in comparison with that of single-injection TAP blocks is not clear. This randomized, triple-blind, placebo-controlled trial investigated the benefits of adding continuous TAP blocks to single-injection TAP blocks after a laparotomy.
Methods. Eighty consecutive patients undergoing midline laparotomy for gynaecological cancer were randomized and received bilateral TAP infusions with either ropivacaine 0.1% (n=40, Rop group) or normal saline (n_40, NS group) at 10 ml h-1 per side for 50 h after surgery. After surgery, bilateral oblique subcostal TAP blocks were performed using ropivacaine 0.1%, 50 ml per side, and then catheters were threaded into the bilateral TAPs. Subsequently, continuous TAP infusions and patient-controlled ix. morphine administration were initiated. The primary outcome was cumulative morphine consumption by 24 h after TAP catheter placement. Secondary outcomes included pain scores, postoperative nausea and vomiting severity, and time to first ambulation and flatus.
Results. The cumulative morphine consumption (median [interquartile range]) 24h after TAP catheter placement was lower in the Rop group (0.25 [0.11-0.48] mg kg 1) than in the NS group (0.44 [0.24-0.73] mg kg 1; 95% confidence interval difference in medians, 0.30 to 0.03; P=0.01). No statistically significant differences were observed in the secondary outcomes, except for reduced pain scores in the Rop group obtained during coughing 1 and 24 h after TAP catheter placement.
Conclusions. Addition of continuous TAP blocks to single-injection TAP blocks reduces pain and morphine consumption after a laparotomy for gynaecological cancer. Clinical trial registration. UMIN Clinical Trials Registry identification number UMIN000013449 (http://www.umin.ac.jp/ctr/ index.htm).

File： Yoshida(2016,BJA).pdf

DOI： 10.1093/bja/aew339

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Pregabalin is thought to exert its therapeutic effect in neuropathic pain via binding to alpha 2 delta - 1 subunits of voltage-gated calcium (Ca2+) channels. However, the exact analgesic mechanism after its binding to alpha 2 delta - 1 subunits remains largely unknown. Whether a clinical concentration of pregabalin ( 10 uM) can cause acute inhibition of dorsal horn neurons in the spinal cord is controversial. To address this issue, we undertook intracellular Ca2+-imaging studies using spinal cord slices with an intact attached L5 dorsal root, and examined if pregabalin acutely inhibits the primary afferent stimulation-evoked excitation of dorsal horn neurons in normal rats and in rats with streptozotocin-induced painful diabetic neuropathy. Under normal conditions, stimulation of a dorsal root evoked Ca2+ signals predominantly in the superficial dorsal horn. Clinically relevant (10 mu M) and a very high concentration of pregabalin (100 pM) did not affect the intensity or spread of dorsal root stimulation-evoked Ca2+ signals, whereas an extremely high dose of pregabalin (300 mu M) slightly but significantly attenuated Ca2+ signals in normal rats and in diabetic neuropathic (DN) rats. There was no difference between normal rats and DN rats with regard to the extent of signal attenuation at all concentrations tested. These results suggest that the activity of dorsal horn neurons in the spinal cord is not inhibited acutely by clinical doses of pregabalin under normal or DN conditions. It is very unlikely that an acute inhibitory action in the dorsal horn is the main analgesic mechanism of pregabalin in neuropathic pain states. (C) 2016 Elsevier B.V. All rights reserved.

File： Pregabalin(2016).pdf

DOI： 10.1016/j.brainres.2016.08.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Hydrogen peroxide (H2O2), a reactive oxygen species, is an important signaling molecule for synaptic and neuronal activity in the central nervous system; it is produced excessively in brain ischemia and spinal cord injury. Although H2O2-mediated modulations of synaptic transmission have been reported in ventral horn (VH) neurons of the rat spinal cord, the effects of H2O2 on neuronal excitability and membrane properties remain poorly understood. Accordingly, the present study investigated such effects using a whole-cell patch-clamp technique. The bath-application of H2O2 decreased neuronal excitability accompanied by decreased input resistance, firing frequency, and action potential amplitude and by increased rheobase. These H2O2-mediated changes were induced by activation of extrasynaptic, but not synaptic, GABA(A) receptors. Indeed, GABAergic tonic currents were enhanced by H2O2. On the other hand, the amplitude of medium and slow afterhyperpolarization (mAHP and sAHP), which plays important roles in controlling neuronal excitability and is mediated by small-conductance calcium-activated potassium (SK) channels, was significantly decreased by H2O2. When extrasynaptic GABA(A) receptors were completely blocked, these decreases of mAHP and sAHP persisted, and H2O2 increased excitability, suggesting that H2O2 per se might have the potential to increase neuronal excitability via decreased SK channel conductance. These findings indicate that activating extrasynaptic GABA(A) receptors or SK channels may attenuate acute neuronal damage caused by H2O2-induced hyperexcitability and therefore represent a novel therapeutic target for the prevention and treatment of H2O2-induced motor neuron disorders. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

File： Ohashi M(Neuroscience,2016).pdf

DOI： 10.1016/j.neuroscience.2016.06.033

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This is the first case report describing the epidural misplacement of an infusion catheter, which was intended to be located in the thoracic paravertebral space using an ultrasound-guided technique. The patient was a 57-year-old female undergoing a laparoscopy-assisted left partial nephrectomy. Before surgery, a Tuohy needle was inserted into the paravertebral space at the left ninth intercostal space using an in-plane transverse ultrasound-guided approach in the lateral-to-medial direction. A catheter was then threaded into the paravertebral space through the needle. Subsequently, the catheter position was secured, although ultrasound-guided confirmation of air injected through the catheter into the paravertebral space was not obtained. Twenty milliliters of 0.5 % levobupivacaine was administered through the catheter at both the initiation and conclusion of surgery. A neurologic examination following surgery revealed paraplegia, along with sensory deficits in the bilateral T3-S5 dermatome. The motor dysfunction in the lower extremities lasted 7 h, and the sensory block lasted 13.5 h. Postoperative radiologic confirmation of the catheter position concomitant with the spread of radiopaque dye revealed that the tip of the catheter was lying in the epidural space. Unless precise attention is paid to detection of the catheter tip location, a thoracic paravertebral catheter can enter into the epidural space even under ultrasound guidance.

File： Yoshida(2016,J Anes).pdf

DOI： 10.1007/s00540-016-2170-9

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Emergence delirium (ED) is a common postoperative complication of ambulatory pediatric surgery done under general anesthesia with sevoflurane. However, perioperative analgesic techniques have been shown to reduce sevoflurane-induced ED. The primary objective of this investigation was to examine whether an ultrasound-guided ilioinguinal/iliohypogastric (II/IH) nerve block for ambulatory pediatric inguinal hernia repair could reduce the incidence of sevoflurane-induced ED.
The subjects of this prospective randomized double-blind study were 40 boys ranging in age from 1 to 6 years, who were scheduled to undergo ambulatory inguinal hernia repair. The patients were randomized to either receive or not to receive an ultrasound-guided II/IH nerve block (Group B and Group NB, respectively). General anesthesia was maintained with sevoflurane and nitrous oxide. The primary outcome assessed was ED, evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale 30 min after emergence from general anesthesia. The secondary outcomes assessed were postoperative pain, evaluated using the Behavioral Observational Pain Scale (BOPS), and the amount of intra-operative sevoflurane given.
The median PAED scale scores did not differ between Groups B and NB at 30 min (P = 0.41). BOPS scores also did not differ significantly between the groups, but the mean amount of intraoperative sevoflurane given was significantly lower in Group B than in Group NB (P &lt; 0.01).
Ultrasound-guided II/IH nerve block for ambulatory pediatric inguinal hernia repair did not reduce ED, but it did decrease the amount of intra-operative sevoflurane needed.
Clinical Trial Registration: UMIN000008586.

File： 大橋（Surg Tuday,2016).pdf

DOI： 10.1007/s00595-015-1280-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.

File： Kurabe(2016,SciRep).pdf

DOI： 10.1038/srep26253

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

To examine whether the consumption of dried bonito both is effective for the prevention of hand-foot syndrome (HFS), concentrated bonito broth was administered to 10 patients with HCC who were treated with sorafenib. Among the 10 patients, seven showed an increase in peripheral blood flow, as observed on Doppler ultrasonography. Only one patient showed Grade 1 HFS on day 14 after the initiation of sorafenib (10%)
this incidence rate of HFS was significantly lower than that obtained in our previous studies and reported data. These results suggest that consumption of dried bonito broth contributes to the prevention of HFS by maintaining peripheral blood flow.

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We describe a case in which an anatomic diagnosis was useful for diagnosing and estimating the cause of femoral nerve palsy following gynecologic surgery. A 49-year-old female received general and epidural anesthesia for radical ovarian cancer surgery. Although injection pain was noted in the left medial shin with 1 % mepivacaine administered as a test dose, the catheter was left indwelling because it improved her symptoms. The surgery, which lasted 195 min, was performed in the lithotomy position, and a self-retained retractor was used to gain a good surgical field. Postoperatively, the patient complained of difficulty in stretching her knee joint and left lower limb paresthesia that did not improve after stopping continuous epidural administration. A spinal cord injury related to epidural anesthesia was suspected because the sites of sensory impairment and epidural injection pain were the same; however, the patient had greater weakness of the quadriceps muscle than the iliopsoas, and no other muscle weakness was observed. These findings and previous reports suggest that her femoral nerve palsy was caused by compression of the inguinal ligament from the self-retaining retractor and lithotomy position. Twenty months after surgery, her muscle strength had fully recovered.

File： Watanabe T(JA,2016) .pdf

DOI： 10.1007/s00540-015-2113-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

We evaluated an alternative technique for ultrasound-guided proximal level obturator nerve block that might facilitate needle visualisation using in-plane ultrasound guidance. Twenty patients undergoing transurethral bladder tumour resection requiring an obturator nerve block were enrolled into a prospective observational study. With the patient in the lithotomy position, the transducer was placed on the medial thigh along the extended line of the inguinal crease, and aimed cephalad to view a thick fascia between the pectineus and obturator externus muscles that contains the obturator nerve. A stimulating nerve block needle was inserted at the pubic region and advanced in-plane with the transducer in an anterior-to-posterior direction. Eight ml levobupivacaine 0.75% was injected within the fascia. The median (IQR [range]) duration for ultrasound identification of the target and injection were 8.5 (7-12 [5-24]) s and 62 (44.5-78.25 [39-383]) s, respectively. All blocks were successful. A cadaver evaluation demonstrated that the dye injected into the target fascia using our technique travelled retrogradely through the obturator canal, and surrounded the anterior and posterior branches of the obturator nerve both proximally and distally to the obturator canal. We believe that this is a promising new technique for ultrasound-guided proximal level obturator nerve block.

File： Yoshida(Anaesthesia,2016).pdf

DOI： 10.1111/anae.13336

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本疼痛学会  

トラネキサム酸(TXA)の脊髄後角を介する痛みの機序について検討した。6〜8週齢のWistar系成熟雄性ラットを用いた。腰部脊椎(L4/5)を椎弓切除し、脊髄クモ膜下にポリエチレンカテーテルを留置した。脊髄クモ膜下投与は、術後3日以上経過してから、カテーテルより濃度の異なるTXAを投与した。腹腔内投与は、直接腹腔内へ濃度の異なるTXAを投与した。TXAは大脳皮質だけではなく、脊髄後角ニューロンへも作用し、シナプス後性にGABAAおよびグリシン受容体を直接的に抑制することで痛みを誘発した。TXAは、一次求心性線維のシナプス前終末には作用せず、興奮性介在ニューロンのGABAAおよびグリシン受容体をシナプス後性に抑制することで脱抑制を生じ、間接的に記録SGニューロンへの興奮性伝達を増強することで痛みを誘発した。TXAの灌流投与により脊髄後角浅層のpERKの発現が増加した。

File： Pain Research(2016).pdf

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Key points Excessive production of reactive oxygen species (ROS) is implicated in many central nervous system disorders; however, the physiological role of ROS in spinal ventral horn (VH) neurons remains poorly understood. We investigated how pathological levels of H2O2, an abundant ROS, regulate synaptic transmission in VH neurons of rats using a whole-cell patch clamp approach. H2O2 increased the release of glutamate and GABA from presynaptic terminals. The increase in glutamate release involved N-type voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inositol trisphosphate receptors (IP(3)Rs); the increase in GABA release, which inhibited glutamatergic transmission, involved IP3R. Inhibiting N-type VGCCs and RyRs attenuates excitotoxicity resulting from increased glutamatergic activity while preserving the neuroprotective effects of GABA, and may represent a novel strategy for treating H2O2-induced motor neuron disorders resulting from trauma or ischaemia-reperfusion injury.
AbstractExcessive production of reactive oxygen species (ROS) is a critical component of the cellular and molecular pathophysiology of many central nervous system (CNS) disorders, including trauma, ischaemia-reperfusion injury, and neurodegenerative diseases. Hydrogen peroxide (H2O2), an abundant ROS, modulates synaptic transmission and contributes to neuronal damage in the CNS; however, the pathophysiological role of H2O2 in spinal cord ventral horn (VH) neurons remains poorly understood, despite reports that these neurons are highly vulnerable to oxidative stress and ischaemia. This was investigated in the present study using a whole-cell patch clamp approach in rats. We found that exogenous application of H2O2 increased the release of glutamate from excitatory presynaptic terminals and -aminobutyric acid (GABA) from inhibitory presynaptic terminals. The increase of glutamate release was induced in part by an increase in Ca2+ influx through N-type voltage-gated calcium channels (VGCCs) as well as by ryanodine receptor (RyR)- and inositol trisphosphate receptor-mediated Ca2+ release from the endoplasmic reticulum (ER). In inhibitory presynaptic neurons, increased IP3R-mediated Ca2+ release from the ER increased GABAergic transmission, which served to rescue VH neurons from excessive release of glutamate from presynaptic terminals. These findings indicate that inhibiting N-type VGCCs or RyRs may attenuate excitotoxicity resulting from increased glutamatergic activity while preserving the neuroprotective effects of GABA, and may therefore represent a novel and targeted strategy for preventing and treating H2O2-induced motor neuron disorders.
Key points Excessive production of reactive oxygen species (ROS) is implicated in many central nervous system disorders; however, the physiological role of ROS in spinal ventral horn (VH) neurons remains poorly understood. We investigated how pathological levels of H2O2, an abundant ROS, regulate synaptic transmission in VH neurons of rats using a whole-cell patch clamp approach. H2O2 increased the release of glutamate and GABA from presynaptic terminals. The increase in glutamate release involved N-type voltage-gated calcium channels (VGCCs), ryanodine receptors (RyRs), and inositol trisphosphate receptors (IP(3)Rs); the increase in GABA release, which inhibited glutamatergic transmission, involved IP3R. Inhibiting N-type VGCCs and RyRs attenuates excitotoxicity resulting from increased glutamatergic activity while preserving the neuroprotective effects of GABA, and may represent a novel strategy for treating H2O2-induced motor neuron disorders resulting from trauma or ischaemia-reperfusion injury.

File： Ohashi M(JP,2016).pdf

DOI： 10.1113/JP271449

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Background: Maternal uniparental disomy 14 (UPD(14)mat) is an imprinting disorder. It is a rare disease, but there is the possibility that more undiagnosed patients might exist because the clinical features of UPD(14)mat resemble those of the Prader-Willi syndrome or other congenital diseases. We performed anesthetic management for an 8-year-old girl with UPD(14)mat. Case presentations: She was admitted to undergo correction surgery due to symptomatic scoliosis. Preoperative examination revealed that she had a restricted mouth opening and retrognathia, as well as some typical characteristics of UPD(14)mat, such as small hands, growth retardation, and precocious puberty. We induced general anesthesia using sevoflurane without any problems. However, the tracheal intubation was difficult because of the restricted mouth opening. We used the McGRATHR MAC videolaryngoscope to overcome this problem. Conclusions: We speculate that the craniofacial deformity in case of UPD(14)mat patients may lead to difficulty in tracheal intubation.

File： Furutani(JA Cli Rep,2016).pdf

DOI： 10.1186/s40981-016-0051-8

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Pain Clinicians  

We report a case of successful pulsed radiofrequency stimulation of the pudendal nerve for pudendal neuralgia. A 70-year-old woman suffered from perineal pain for 3 months. The pain was predominantly experienced only in the sitting position. She experienced tenderness by palpation of the bilateral ischial spine. After diagnosis with pudendal neuralgia according to Nantes Criteria, she was treated with the pulsed radio frequency of the pudendal nerve, and the pain was well controlled.

File： 清水（ペイン学会誌,2016).pdf

DOI： 10.11321/jjspc.16-0013

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A patient with medication resistant schizophrenia underwent modified electroconvulsive therapy (12 sessions). Propofol was chosen as a hypnotic agent and the adjustment of its dose and stimulus intensity was attempted. However, despite using propofol of a dose minimally required for hypnosis, adequate seizures could not be induced even with the maximum stimulation. Assuming that propofol was preventing the induction of seizures, it was decided to reduce its dose and at the same time to combine it with remifentanil 100 μg starting from the fifth session. This allowed to reach the seizure adequacy during the next and the four subsequent sessions. Although from the tenth session on, adequate seizures could no longer be induced (possibly due to the development of resistance to propofol), the patient's symptoms showed improvement after completion of all 12 sessions.

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File： Hiruma(Can J Anes,2015.pdf

DOI： 10.1007/s12630-015-0400-5

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Monoacylglycerol lipase (MGL) is a major enzyme involved in degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG). Selective inhibitors of MGL are regarded as promising analgesics and anticancer agents. To gain insight into the possible consequences of their prolonged administration for anesthetic action, the effects of several inhalational and intravenous anesthetics were tested in knockout mice lacking the MGL gene in the loss of righting reflex (LORR) assay, Sensitivity to inhalational and most intravenous anesthetics was not altered in knockout mice. However, compared with wild-type litter-mates, they showed increased sensitivity to the intravenous anesthetic propofol. Permanently elevated levels of 2-AG after MGL knockout are known to cause desensitization of cannabinoid (CB1) receptors, which have been advocated as possible mediators of propofol anesthesia. Therefore, increased sensitivity to propofol in knockout mice at first suggested that 2-AG may potentiate CBI receptors despite their hypofunction in these animals. Pharmacologic inhibition of MGL also causes desensitization of CB1 receptors, so sensitivity to propofol was tested further in C57BL/6N mice pretreated chronically with the selective MGL inhibitor JZL 184. Contrary to the results in knockout mice, these animals showed drastically reduced sensitivity to propofol. The reason for increased sensitivity to propofol after MGL knockout remains unclear, but may result from changes occurring in these animals during development. However, our results in C57BL/6N mice pretreated with JZL 184 confirmed the role of CB1 receptors in propofol anesthesia advocated previously, and also suggest that prolonged use of MGL inhibitors may be associated with the development of resistance to propofol. (C) 2015 Elsevier B.V. All rights reserved.

File： Petrenko(Eur J Pharm,2015).pdf

DOI： 10.1016/j.ejphar.2015.08.048

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63歳男。28歳時に統合失調症と診断され、以後入退院を繰り返していた。今回、妄想などの症状が増悪したため当院精神科に入院したが、薬物療法に抵抗性のため修正型電気痙攣療法(mECT)の適用となった。mECT施行時に睡眠最低必要量のプロポフォール投与下で最大刺激を与えるも十分な痙攣が誘発されなかった。そこで、レミフェンタニルを併用し、プロポフォール投与量を減量したところ、有効な痙攣を誘発することができた。mECTを12回施行し、簡易精神医学的評価尺度は50点から22点に改善した。

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Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood loss during surgery. However, a serious adverse effect of TXA is seizure due to inhibition of gamma-aminobutyric acid (GABA) and glycine receptors in cortical neurons. These receptors are also present in the spinal cord, and antagonism of these receptors in spinal dorsal horn neurons produces pain-related phenomena, such as allodynia and hyperalgesia, in experimental animals. Moreover, some patients who are injected intrathecally with TXA develop severe back pain. However, the effect of TXA on spinal dorsal horn neurons remain poorly understood. Here, we investigated the effects of TXA by using behavioral measures in rats and found that TXA produces behaviors indicative of spontaneous pain and mechanical allodynia. We then performed whole-cell patch-clamp experiments that showed that TXA inhibits GABA(A) and glycine receptors in spinal dorsal horn neurons. Finally, we also showed that TXA facilitates activation of the extracellular signal-regulated kinase in the spinal cord. These results indicated that TXA produces pain by inhibiting GABA(A) and glycine receptors in the spinal dorsal horn.

File： Ohashi(Sci Rep,2015).pdf

DOI： 10.1038/srep13458

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File： Ishii (EJA,2015).pdf

DOI： 10.1097/EJA.0000000000000258

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Transient ischemia produces postischemic tingling sensation. Ischemia also produces nerve conduction block that may modulate spinal neural circuits. In the present study, reduced mechanical thresholds for hindpaw-withdrawal reflex were found in mice after transient hindpaw ischemia, which was produced by a high pressure applied around the hindpaw for 30 min. The reduction in the threshold was blocked by spinal application of LY354740, a specific agonist of group II metabotropic glutamate receptors. Neural activities in the spinal cord and the primary somatosensory cortex (S-1) were investigated using activity-dependent changes in endogenous fluorescence derived from mitochondrial flavoproteins. Ischemic treatment induced potentiation of the ipsilateral spinal and contralateral S-1 responses to hindpaw stimulation. Both types of potentiation were blocked by spinal application of LY354740. The contralateral S-1 responses, abolished by lesioning the ipsilateral dorsal column, reappeared after ischemic treatment, indicating that postischemic tingling sensation reflects a sensory modality shift from tactile sensation to nociception in the spinal cord. Changes in neural responses were investigated during ischemic treatment in the contralateral spinal cord and the ipsilateral S1. Potentiation already appeared during ischemic treatment for 30 min. The present findings suggest that the postischemic potentiation shares spinal mechanisms, at least in part, with neuropathic pain.

File： Watanabe (Sci Rep,2015).pdf

DOI： 10.1038/srep11191

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File： Watanabe(Can J Anes,2015).pdf

DOI： 10.1007/s12630-015-0331-1

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トラネキサム酸(TXA)の痛みに対する作用・機序について検討するため、まずラットを用いて行動学実験を行った。クモ膜下腔に留置したカテーテルよりTXAを投与して自発痛様行動を観察した結果、その持続時間は濃度依存性に延長した。次に電気生理学的実験として、脊髄後角膠様質細胞を用いてホールセルパッチクランプ記録を行い、TXAの灌流投与に対する自発性抑制性シナプス後電流(sIPSC)の反応を調べた。sIPSCの振幅はTXA投与により減少し、頻度は変化がなかった。またグリシン受容体拮抗薬のstrychnineまたはガンマアミノ酪酸(GABA)受容体拮抗薬のbicucullineを灌流投与したところ、strychnine存在下ではGABA作動性sIPSC、bicuculline存在下ではグリシン作動性sIPSCの振幅は減少した。TXAは脊髄後角ニューロンのGABAおよびグリシン受容体をシナプス後性に抑制し、それによって自発痛を増強させる可能性が示唆された。

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静脈投与したリドカインの鎮痛作用の機序について、リドカインが脊髄後角ニューロンにおける興奮性シナプス伝達を修飾しているとの仮説を立て、成熟ラットの脊髄標本を用いてブラインドホールセルパッチクランプ記録による検討を行った。その結果、自発性興奮性シナプス後電流(EPSC)の発生頻度はリドカイン投与により減少し、濃度依存的、可逆的な変化を示した。振幅に関しては有意な変化がなかった。またpinch刺入による誘発性EPSCもリドカイン投与により抑制された。リドカインを脊髄表面に灌流投与した場合は、自発性EPSCの頻度・振幅とも変化はなかった。リドカインは脊髄後角ニューロンにおいてシナプス前終末からのグルタミン酸の放出を抑制し、その結果として脳への痛覚伝達が抑制され、鎮痛作用を発揮している可能性が示唆された。

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脊髄前角ニューロンに対する過酸化水素(H2O2)の作用機序について検討するため、ラット脊髄横断スライスを用いてホールセルパッチクランプ記録を行った。まずグルコン酸カリウムベースの電極内液を用い、保持膜電位-70mVの条件下でH2O2を灌流投与したところ、外向き電流が誘起された。その振幅はH2O2の繰り返し投与による変化は認めず、K+チャネル阻害薬であるセシウム(Cs)およびtetraethylammoniumを含んだ電極内液で有意に抑制された。またCsベースの電極内液を用いて自発性興奮性シナプス後電流の頻度と振幅を調べたところ、H2O2の灌流投与により振幅は有意な変化を認めず、頻度は一過性に増加した後に減少に転じ、減少は遷延した。電位依存性Na+チャネル阻害薬であるテトロドトキシン存在下でも、微小興奮性シナプス後電流が同様の変化を示した。

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File： Shimizu(JA Cli Report,2015).pdf

DOI： 10.1186/s40981-015-0023-4

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Background: Acute postoperative pain is an integral risk factor in the development of chronic pain after breast cancer surgery (BCS). Pectoral nerve block (PECSB) has been recently reported as an analgesic method for BCS. Here, we retrospectively compared intraoperative opioid requirement, postoperative pain after BCS, and incidence of postoperative nausea and vomiting (PONV) in patients who underwent BCS under total intravenous anesthesia (TIVA) with or without PECSB. Findings: We reviewed anesthesia charts and medical records of 146 patients who underwent BCS at Niigata University Medical and Dental Hospital from January 2013 to March 2014; 36 patients were included in the TIVA group, and 35 patients were included in the TIVA + PECSB group. Intraoperative remifentanil requirements were significantly lower in the TIVA + PECSB group than in the TIVA group, and the cumulative distribution of remifentanil was reduced in patients who received PECSB (TIVA: 10.9 ± 2.9 μg/kg/h; TIVA + PECSB: 7.3 ± 3.3 μg/kg/h; p < 0.001). Postoperative pain scores during the 48 h after surgery were significantly lower in the TIVA + PECSB group than in the TIVA group (TIVA: 2 [1-5]; TIVA + PECSB: 1 [0-5]; p = 0.03). However, administration of fentanyl during operation, percentage of patients requiring supplemental analgesics, and incidence of PONV were not significantly different between groups. Conclusions: PECSB significantly reduced intraoperative remifentanil usage and postoperative pain. However, the requirement for postoperative supplemental analgesics and the incidence of PONV did not differ. These data suggested that PECSB may be useful for perioperative pain management in patients undergoing BCS.

File： Morioka (JA CR, 2015).pdf

DOI： 10.1186/s40981-015-0018-1

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Opioid-induced spastic paraplegia after transient spinal cord ischemia during aortic surgery has been reported. Opioids modulate neurotransmission through mu (mu) opioid receptors (MORs) in the spinal ventral horn. However, their effects during ischemic insult are not understood.
The effects of the selective mu agonist [d-Ala(2),-N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO) on ischemia-induced agonal currents were examined in the spinal lamina IX neurons of neonatal rats by using the whole-cell patch-clamp technique. Ischemia was simulated in vitro by oxygen/glucose deprivation.
DAMGO (1 mu M) produced outward currents in similar to 60 % of spinal lamina IX neurons at a holding potential of -70 mV. Superfusion with ischemia-simulating medium elicited an agonal current. The latency was 457 +/- A 18 s. Despite its neuromodulatory effects, DAMGO did not significantly change the latencies of the agonal currents with (440 +/- A 23 s) or without (454 +/- A 33 s) DAMGO-induced currents.
Activation of MORs does not influence ongoing ischemia-induced neuronal death. Our findings indicate that MOR agonist administration should be suitable as an anesthetic during aortic surgery.

File： Honda(JA,2014).pdf

DOI： 10.1007/s00540-014-1829-3

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File： Petrenko(A&A,2014).pdf

DOI： 10.1213/ANE.0000000000000391

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Monoacylglycerol lipase (MGL) is the main enzyme responsible for degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG). Selective inhibitors of MGL have antinociceptive effects upon acute administration and, therefore, hold promise as analgesics. To gain insight into the possible consequences of their prolonged administration, genetically modified mice with the knocked-out MGL gene were tested in several models of acute (phasic, tonic) and chronic (inflammatory, neuropathic) pain. MGL knockout mice showed normal acute phasic pain perception (pain thresholds) and no alleviation of pain perception in models of inflammatory and neuropathic pain. However, compared with wild-type controls, they showed significantly augmented nociceptive behavior in models of acute somatic and visceral tonic pain (formalin and acetic acid tests). The observed proalgesic changes in perception of tonic pain in MGL knockouts could have resulted from desensitization of cannabinoid receptors (known to occur after genetic inactivation of MGL). Supporting this notion, chronic pretreatment with the selective CBI receptor antagonist AM 251 (employed to re-sensitize cannabinoid receptors in MGL knockouts) resulted in normalization of their tonic pain-related behaviors. Similar augmentation of tonic pain-related behaviors was replicated in C57BL/6N mice pretreated chronically with the selective MGL inhibitor JZL 184 (employed to pharmacologically desensitize CB1 receptors). These findings imply that prolonged use of MGL inhibitors, at doses causing close to complete inhibition of MGL enzymatic activity, not only have no beneficial analgesic effects, they may lead to exacerbation of some types of pain (particularly those with a tonic component). (C) 2014 Elsevier B.V. All rights reserved.

File： Petrenko(Behav Rrain Res,2014).pdf

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File： Watanabe(JA,2014).pdf

DOI： 10.1007/s00540-013-1707-4

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Factors affecting the distribution of continuous thoracic paravertebral block have never been examined. We designed this prospective, double-blind study to check whether continuous thoracic paravertebral block with a higher ropivacaine concentration would provide a wider segmental sensory block spread. Sixty consecutive patients undergoing pulmonary lobectomy or segmentectomy were randomly allocated to receive continuous paravertebral infusion of either 0.2% or 0.5% ropivacaine (6ml.h(-1)). The primary outcome was the number of anaesthetised dermatomes as determined by loss of cold sensation 24h after surgery. Twenty-seven patients per group were included in the final analysis. The median (IQR [range]) number of anaesthetised dermatomes 24h after surgery was 4 (3-6 [1-9]) with ropivacaine 0.2% and 4 (3-6 [2-11]) with ropivacaine 0.5% (p=0.66). Contrary to our expectation, the segmental spread of sensory block produced by continuous thoracic paravertebral block does not depend on ropivacaine concentration.

DOI： 10.1111/anae.12531

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File： Petrenko(A&A,2014,Hypnotic).pdf

DOI： 10.1213/ANE.0000000000000025

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Introduction. Growing teratoma syndrome is a rare occurrence with an ovarian tumor. Anesthesia has been reported to be difficult in cases of growing teratoma syndrome of the cystic type due to the pressure exerted by the tumor. However, there have been no similar reports with the solid mass type. Here, we report our experience of anesthesia in a case of growing teratoma syndrome of the solid type. Case presentation. The patient was a 30-year-old Japanese woman who had been diagnosed with an ovarian immature teratoma at age 12 and had undergone surgery and chemotherapy. However, she dropped out of treatment. She presented to our hospital with a 40cm giant solid mass and severe respiratory failure, and was scheduled for an operation. We determined that we could not obtain a sufficient tidal volume without spontaneous respiration. Therefore, we chose to perform awake intubation and not to use a muscle relaxant before the operation. At the start of the operation, when muscle relaxant was first administered, we could not obtain a sufficient tidal volume. An abdominal midline incision was performed immediately and her tidal volume recovered. Her resected tumor weighed 10.5kg. After removal of her tumor, her tidal volume was maintained at a level consistent with that under spontaneous respiration to avoid occurrence of re-expansion pulmonary edema. Conclusions: We performed successful anesthetic management of a case of growing teratoma syndrome with a giant abdominal tumor. Respiratory management was achieved by avoiding use of a muscle relaxant before the operation to maintain spontaneous respiration and by maintaining a relatively low tidal volume, similar to that during spontaneous respiration preoperatively, after removal of the tumor to prevent re-expansion pulmonary edema. © 2014Ohashi et al.
licensee BioMed Central Ltd.

File： Ohash(J Med Case Rep,2014).pdf

DOI： 10.1186/1752-1947-8-32

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N-methyl-D-aspartate (NMDA) receptors are important in mediating excitatory neurotransmission in the nervous system. They are preferentially inhibited by some general anesthetics and have, therefore, been implied in the mediation of their effects. This review summarizes the main research findings available related to NMDA receptors and their role in anesthesia. The contribution of NMDA receptors to the anesthetized state is discussed separately for each of its components: amnesia, analgesia, Unconsciousness and immobility. Anesthetic-induced unconsciousness and immobility have received the most attention in the research community and are the main focus of this review. In the overall perspective, however, studies using pharmacological or electrophysiological approaches have Wed to reach definitive conclusions regarding the contribution of NMDA receptors to these anesthetic endpoints. None of the studies have specifically addressed the role of NMDA receptors in the amnestic effect of general anesthetics, and the Few available data are (at best) only indirect. NMDA receptor antagonism by general anesthetics may have a preventive anti-hyperalgesic effect. The only and most extensively used genetic tool to examine the role of NMDA receptors in anesthesia is global knockout of the GluN2A subunit of the NMDA receptor. These animals are resistant to many intravenous and inhalational anesthetics, but the interpretation of their phenotype is hindered by the secondary changes occurring in these animals after GluN2A knockout, which are themselves capable of altering anesthetic sensitivity. Generation of more sophisticated conditional knockout models targeting NMDA receptors is required to finally define their role in the mechanisms of anesthesia. (C) 2013 Elsevier B.V. All rights reserved.

File： Petrenko(Eur J Pharmacol,2014).pdf

DOI： 10.1016/j.ejphar.2013.11.039

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File： 過酸化水素(Ohashi M,2014).pdf

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File： 大橋（脊髄機能診断,2014）.pdf

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File： ステロイド(Yamamoto G,2014).pdf

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File： リドカイン(2014).pdf

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Congenital myasthenic syndromes (CMS) are heterogeneous disorders of neurotransmission caused by genetic mutations of neuromuscular junction molecules. We report anesthetic management of a CMS patient who was a 14-year-old boy with endplate acetylcholinesterase deficiency. The patient used noninvasive positive pressure ventilation (NPPV) at night He underwent a corrective maneuver for severe scoliosis under general anesthesia. General anesthesia was maintained using propofol and remifentanil. Intraoperative mechanical ventilation remained stable. Extubation was performed on the next day and NPPV was started. Several hours later, he complained of a stomachache and intense abdominal bloating. Computed tomography revealed a massive amount of air in the stomach and intestine. He recovered from abdominal bloating the next day without treatment for decompression. Lung-thoracic compliance has been reported to decrease immediately after a corrective maneuver for scoliosis patients. In our case, we suspected a relative increase of abdominal compliance to lung-thoracic compliance as a cause of intense abdominal bloating by air injection from NPPV with his daily setting. In CMS, symptoms, therapy and contraindicated drugs vary according to the location of dysfunction. Therefore, anesthetic management according to each genotype should be designed to avoid drugs that could either trigger or worsen CMS. Intensive respiratory care is advisable after surgery.

File： 江村美紗（麻酔,2014）.pdf

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File： 大橋（2013）.pdf

DOI： 10.11321/jjspc.12-0045

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DOI： 10.11321/jjspc.12-0036

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Other Link： https://jlc.jst.go.jp/DN/JALC/10021049728?from=CiNii

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Background : We performed a retrospective study of the efficacy and safety of spinal anesthesia with 0.1 mg morphine in the postoperative course of elderly patients with femoral neck fracture. Methods : Sixty patients with ages averaging 84 years participated in this study. Surgery was performed under spinal anesthesia. Patients were assigned to either a group receiving of 0.1 mg morphine added to isobaric bupivacaine (Group M) or a group receiving of isobaric bupivacaine alone (Group B). The frequency of analgesic use and the occurrence of adverse side effects during the first 48 hours after surgery were compared between the two groups. Results : In the first 24 hours, the patients in Group M needed significantly less analgesics compared to Group B. The incidence of adverse side effects did not differ significantly between the groups, although nausea had a tendency to increase in Group M. One patient in Group M showed a mild decrease in oxygen saturation. Conclusions : The spinal administration of 0.1 mg morphine had beneficial effects and was safe in the postoperative period of elderly patients with femoral neck fracture provided that sufficient observation was given.

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Background: Acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) are undesirable effects of opioids that have been reported in both animals and humans. However, the development of AOT and OIH in cases of potent, short-acting mu-opioid receptor agonist remifentanil administration remains controversial. It has been suggested that the emergence of AOT and OIH by remifentanil could be dose and infusion duration dependent, i.e., low dose and short infusions may lead to negative results. In this study, we determined whether AOT and OIH could be elicited by prolonged, continuous administration of remifentanil at maximally tolerable doses in C57BL/6 mice.
Results: The analgesic effects of continuously administered remifentanil [by short (1 h) and prolonged (4 h) intraperitoneal infusions] were studied. These experiments involved repeated measurements of thermal thresholds during remifentanil administration. Therefore, particular attention was paid to prevent cumulative tissue injury, which could mimic pronociceptive effects of remifentanil. To exclude the possibility of pseudoAOT during infusion, we used brief cooling of all ipsilateral hindpaws that exhibited analgesic response. Thermal thresholds remained steadily elevated over a 1-h period during continuous administration at infusion rates of 120, 180, and 240 mg/kg/h, which indicated no AOT development. To exclude the possibility of pseudoOIH after infusion, intact contralateral hindpaws were used for all postinfusion threshold measurements. Thermal thresholds at each infusion rate returned to the baseline values within 15 min after the termination of the administration. They did not decrease below the baseline values during 1 h following infusion, which indicated no OIH development. Similar threshold dynamics were also observed for thermal and mechanical testing modalities in animals infused at 120 mg/kg/h for 4 h as well as in animals with rapidly attained and maintained maximum analgesia for 3 h.
Conclusions: These results suggest that neither intra-infusion AOT nor postinfusion OIH develops in mice receiving continuous remifentanil when the possibility of cumulative tissue injury mimicking AOT or OIH is carefully avoided.

File： Ishii(Mol Pian, 2013).pdf

DOI： 10.1186/1744-8069-9-11

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N-methyl-D-aspartate (NMDA) receptors can be inhibited by inhalational anesthetics in vitro at clinically relevant concentrations. Here, to clarify the role of NMDA receptors in anesthetic-induced unconsciousness, we examined the hypnotic properties of isoflurane, sevoflurane and nitrous oxide in NMDA receptor GluN2A subunit knockout mice. The hypnotic properties of inhalational anesthetics were evaluated in mice in the loss of righting reflex (LORR) assay by measuring the 50% concentration for LORR (LORR ED50). Knockout mice displayed isoflurane and sevoflurane LORR ED50 values similar to wild-type controls, indicating no significant contribution of these receptors to the hypnotic action of halogenated anesthetics. However, compared with wild-type controls, mutant mice displayed larger isoflurane LORR ED50 values in the presence of nitrous oxide, indicating a resistance to this gaseous anesthetic. Knockout mice have enhanced brain monoaminergic activity which occurs secondary to NMDA receptor dysfunction, and the observed resistance to the isoflurane LORR ED50-sparing effect of nitrous oxide could be abolished by pretreatment with the dopamine D-2 receptor antagonist droperidol or with the serotonin 5-HT (2A), receptor antagonist ketanserin. Thus, resistance to nitrous oxide in knockout mice appears to be a secondary phenomenon of monoaminergic origin and not a direct result of impaired NMDA receptor function. Our results indicate that NMDA receptors are not critically involved in the hypnotic action of conventionally-used inhalational anesthetics. Also, they suggest that increased brain monoaminergic tone can diminish the effects of general anesthesia. Finally, they provide further evidence that changes secondary to genetic manipulation can explain the results obtained in global knockouts. (C) 2012 Elsevier B.V. All rights reserved.

File： Petrenko(Eur J Pharmacol,2013).pdf

DOI： 10.1016/j.ejphar.2012.10.034

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Language：Japanese   Publisher：JAPANESE ASSOCIATION FOR STUDY OF PAIN  

Tranexamic acid (TXA) is an antifibrinolytic agent widely used to reduce blood loss during surgery. However, a serious adverse effect of TXA is seizure due to inhibition of γ–aminobutyric acid (GABA) and glycine receptors in cortical neurons. These receptors are also present in the spinal cord, and antagonism of these receptors in spinal dorsal horn neurons produces painrelated phenomena, such as allodynia and hyperalgesia. Moreover, some patients who are injected intrathecally with TXA develop severe back pain. However, no previous studies have investigated whether TXA modulates the GABA and glycine receptors in dorsal horn neurons. We hypothesized that TXA inhibits both GABA and glycine receptors in dorsal horn neurons,resulting in producing pain. Here, we investigated the effects of TXA by using behavioral measures in rats and found that TXA produces behaviors indicative of spontaneous pain and allodynia. We then performed wholecell patch–clamp experiments that showed that TXA inhibits GABAA and glycine receptors in spinal dorsal horn neurons. Finally, we also showed that TXA facilitates activation of the extracellular signal–regulated kinase in the spinal cord. These results indicated that TXA produces pain by inhibiting GABAA and glycine receptors directly located on postsynaptic sites of the recorded SG neurons. In addition, TXA enhances the excitability of excitatory interneurons via blockade of GABAergic and glycinergic postsynaptic inhibition, which facilitates excitatory transmission to the SG neurons indirectly.

DOI： 10.11154/pain.31.9

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Other Link： http://search.jamas.or.jp/link/ui/2016213404

Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

File： Petrenko(Anesthesiology,2012).pdf

DOI： 10.1097/ALN.0b013e318272d898

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File： Petrenko(A&A,2012).pdf

DOI： 10.1213/ANE.0b013e318263ca5c

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Language：Japanese   Publisher：真興交易(株)医書出版部  

橈骨動脈カニューレの開存性を維持することは重要であるが、ドレッシング材の添付文書(conventional method)に従い固定した場合でも、カニューレの閉塞や圧波形の描出不良をしばしば経験する。この問題を改善するため、新しい固定法(pillow method)を考案した。今回、対象症例102例をランダムにconventional methodとpillow methodに割り当てpillow methodの有効性を検討した。その結果、pillow methodによる固定は動脈カニューレの開存を良好に維持することができ、より細いカニューレでも安定した動脈圧モニタリングが行えることが示唆された。(著者抄録)

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BACKGROUND: Opioids inhibit excitatory neurotransmission and produce antinociception through mu opioid receptors (MORs). Although MORs are expressed in the spinal ventral horn, their functions and effects are largely unknown. Therefore, we examined the neuromodulatory effects of mu opioids in spinal lamina IX neurons at the cellular level.
METHODS: The effects of the selective mu agonist [D-Ala(2),-N-Me-Phe(4), Gly(5)-ol]Jenkephalin (DAMGO) on synaptic transmission were examined in spinal lamina IX neurons of neonatal rats using the whole-cell patch-clamp technique.
RESULTS: DAMGO produced outward currents in 56% of the lamina IX neurons recorded, with a 50% effective concentration of 0.1 mu M. Analysis of the current-voltage relationship revealed a reversal potential of approximately -86 mV. These currents were not blocked by tetrodotoxin but were inhibited by Ba2+ or a selective mu antagonist. Moreover, the currents were suppressed by the addition of Cs+ and tetraethylammonium or guanosine 5'-[beta-thi]diphosphate trilithium salt to the pipette solution. In addition, DAMGO decreased the frequency of spontaneous excitatory and inhibitory postsynaptic currents, and these effects were unaltered by treatment with tetrodotoxin.
CONCLUSION: Our results suggest that DAMGO hyperpolarizes spinal lamina IX neurons by G protein-mediated activation of K+ channels after activation of MORs. Furthermore, activation of MORs on presynaptic terminals reduces both excitatory and inhibitory transmitter release. Although traditionally opioids are not thought to affect motor function, the present study documents neuromodulatory effects of mu opioids in spinal lamina IX neurons, suggesting that MORs can influence motor activity. (Anesth Analg 2012;115:703-12)

File： Honda(A & A,2012).pdf

DOI： 10.1213/ANE.0b013e318259393d

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We report 2 patients for whom anesthetic management using aortic occlusion balloon catheter (AOBC) was performed thrice. A 14-year-old boy and a 43-year-old man with sacral giant cell tumor underwent tumor resection. In both patients, transcatheter arterial embolization (TAE) was performed several times before the operation. Before the surgery, an AOBC was inserted via the right femoral artery. For tumor resection, the AOBC was inflated, and a slight decrease in hemorrhage was observed. The occlusion was maintained for 40-55 min, with a loss of 1,400-3,700 ml of blood. In case 1, moderate bleeding from the epidural venous plexus was observed. In case 2, packed red blood cell transfusion was needed, and the patient returned to surgery for hemostasis. Because the AOBC could not decrease the severity of venous hemorrhage, we expected increased hemorrhage with an increase in the extent of surgery. In addition, preoperative multiple TAE might lead to the development of collateral circulation around the sacrum and augment the amount of blood loss in that region. Although the AOBC could reduce intraoperative hemorrhage, uncontrollable bleeding may occur if the sacral giant cell tumor shows extensive dissemination.

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症例1は14歳男性で、仙骨部の巨細胞腫に対し経カテーテル動脈塞栓術(TAE)を2回行ったが縮小せず、摘出手術となった。腫瘍は仙骨内を占拠し、一部脊柱管内に進展していた。麻酔導入後、出血量制御のため右大腿動脈よりシースを挿入し、大動脈遮断バルーンカテーテル(AOBC)の先端を第2〜3腰椎間に留置した。腫瘍操作直前にバルーンを膨らませ、血栓予防のためヘパリンを静注した。操作が脊柱管に及んだ際に硬膜外静脈叢からの出血が生じたが、閉鎖時間55分、総出血量1390mlで手術を終了した。残存腫瘍に対する再手術も同様に行った。症例2は43歳男性で、仙骨部の巨細胞腫に対しTAEを6回行ったが疼痛が増強し、摘出術を施行した。症例1と同様にAOBCの留置と操作を行ったが、腫瘍切除に伴って比較的大量に出血し、大動脈閉鎖時間50分、総出血量3705mlであった。手術5時間後に神経圧迫症状が出現し血腫除去・止血術を要したが、症状は軽快し退院に至った。

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Background: Antidepressants, which are widely used for treatment of chronic pain, are thought to have antinociceptive effects by blockade of serotonin and noradrenaline reuptake. However, these drugs also interact with various receptors such as excitatory glutamatergic receptors. Thermal hyperalgesia was induced by intrathecal injection of NMDA in rats. Paw withdrawal latency was measured after intrathecal injection of antidepressants. The effects of antidepressants on the NMDA and AMPA-induced responses were examined in lamina II neurons of rat spinal cord slices using the whole-cell patch-clamp technique. The effects of milnacipran followed by application of NMDA on pERK activation were also investigated in the spinal cord.
Results: Intrathecal injection of milnacipran (0.1 mu mol), but not citalopram (0.1 mu mol) and desipramine (0.1 mu mol), followed by intrathecal injection of NMDA (1 mu g) suppressed thermal hyperalgesia. Milnacipran (100 mu M) reduced the amplitude of NMDA (56 +/- 3 %, 64 +/- 5 % of control)-, but not AMPA (98 +/- 5 %, 97 +/- 5 % of control)- mediated currents induced by exogenous application and dorsal root stimulation, respectively. Citalopram (100 mu M) and desipramine (30 mu M) had no effect on the amplitude of exogenous NMDA-induced currents. The number of pERK-positive neurons in the group treated with milnacipran (100 mu M), but not citalopram (100 mu M) or desipramine (30 mu M), followed by NMDA (100 mu M) was significantly lower compared with the NMDA-alone group.
Conclusions: The antinociceptive effect of milnacipran may be dependent on the drug's direct modulation of NMDA receptors in the superficial dorsal horn. Furthermore, in addition to inhibiting the reuptake of monoamines, glutamate NMDA receptors are also important for analgesia induced by milnacipran.

File： Kohno(Mol Pain,2012).pdf

DOI： 10.1186/1744-8069-8-45

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A 26-year-old woman with Ehlers-Danlos syndrome (EDS) underwent posterior spinal fusion with instrumentation for scoliosis. General anesthesia was maintained using propofol and remifentanil. The procedure was performed examining the motor evoked potential (MEP) and somatosensory evoked potential (SSEP) of the lower extremities with the patient placed in the prone position. The procedure was completed successfully without major cardiovascular or respiratory complications. The duration of anesthesia was 821 min. When drapes were removed, we noticed that the right shoulder was in a hyperabduction position. After emergence from anesthesia, it was observed that the right upper extremity was paralyzed. Thereafter, brachial plexus injury, which may have been due to intraoperative malpositioning, was diagnosed. Brachial plexus injury is the most common among the nerve injuries resulting from intraoperative malpositioning. Patients with EDS are thought to be at high risk for the complications and it has also been reported that patients with joint hypermobility, such as that in EDS or Marfan syndrome, are highly susceptible to nerve injury. Intraoperative monitoring of the MEP and SSEP in the upper extremities should be considered for early detection and prevention of brachial plexus injury in patients with EDS who are thought to be at high risk.

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Background: The minimum alveolar concentration is determined in the spinal cord rather than in the brain. Xenon inhibits glutamatergic excitatory synaptic transmission in the dorsal horn neurons. However, its actions in the ventral horn neurons have not been investigated.
Methods: The effects of 50 or 75% xenon on excitatory and inhibitory synaptic transmission were examined in the spinal lamina IX neurons of neonatal rats by using a whole cell patch clamp technique.
Results: Fifty percent xenon inhibited the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid-induced currents (amplitudes = 72 +/- 9% and integrated area = 73 +/- 13% of the control values), and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid receptor-mediated electrically evoked excitatory postsynaptic currents (amplitudes = 69 +/- 13% of the control values). Seventy-five percent xenon similarly inhibited alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid-induced currents. However, xenon had no effect on the N-methyl-D-aspartate-induced currents or N-methyl-D-aspartate receptor-mediated electrically evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There were no discernible effects on the currents induced by gamma-aminobutyric acid or glycine or on miniature inhibitory postsynaptic currents.
Conclusions: Xenon inhibits alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid receptor-mediated glutamatergic excitatory transmission in the spinal lamina IX neurons via a postsynaptic mechanism. In contrast, there are no substantial effects on N-methyl-D-aspartate receptor-mediated or inhibitory synaptic transmission. The suppressive effects on excitatory synaptic transmission in the ventral horn neurons partly account for the mechanism behind xenon's ability to produce immobility in response to noxious stimuli and to determine the minimum alveolar concentration.

File： Yamamoto(Anesthesiology,2012).pdf

DOI： 10.1097/ALN.0b013e31825037a1

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File： Petrenko(Anesthesiology,2012).pdf

DOI： 10.1097/ALN.0b013e318245bfce

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File： Ishii(Anesthesiology,2012).pdf

DOI： 10.1097/ALN.0b013e31823cfaad

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In this report we describe an alternative approach to catheter placement for continuous selective median nerve blockade. It spared the finger movements and therefore allowed early postoperative rehabilitation in a patient who underwent surgical repair of the index finger flexor tendon.
A patient with a complicated history of traumatic index finger flexor tendon rupture, surgical repair, failed rehabilitation due to poor postoperative pain control, adhesion formation, and subsequent rerupture due to tenolysis was admitted for reconstructive surgery. This time, a continuous regional block was used. Although the insertion of a catheter at the wrist level would have spared the anterior interosseous branch of the median nerve and preserved finger movements, a more distant site had to be chosen to avoid proximity to the surgical wound. Therefore, under combined ultrasonography and neurostimulation guidance, the catheter was inserted in the proximal one-third of the patient's forearm distal to the branching-off point of the anterior interosseous nerve. Continuous ropivacaine infusion was initiated and maintained until being stopped on the afternoon of the third postoperative day, providing good analgesia without interfering with postoperative physiotherapy, which was successfully completed during this hospitalization.
Placement of a catheter for continuous median nerve blockade in the proximal one-third of the forearm for effective postoperative pain-free rehabilitation after hand surgery should be considered in cases in which the surgical incision extends toward the patient's wrist. The block site can be readily identified by a combined use of ultrasonography and neurostimulation guidance.

File： Watanabe(Can J Anes,2012).pdf

DOI： 10.1007/s12630-011-9613-4

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File： 日本臨床麻酔学会誌.32.大西2012.pdf

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Low preoperative left ventricular ejection fraction (EF) is a predictor of the need for inotropic support after cardiac surgery. However, EF can be misinterpreted and difficult to measure in some cases. The purpose of this study was to compare the value of preoperative EF and intraoperative tissue Doppler imaging variables in predicting the need for postoperative inotropic support.
Forty-eight consecutive adult patients undergoing cardiac surgery were enrolled in this study. Systolic mitral annular velocity (S (m)), early diastolic mitral annular velocity (E (m)), the ratio of E (m) to late diastolic mitral annular velocity (E (m)/A (m)), and the ratio of early diastolic transmitral velocity to E (m) (E/E (m)) were measured using transesophageal echocardiography before median sternotomy. The primary outcome was the need for inotropic support for 12 or more hours after surgery. Preoperative, intraoperative, and echocardiographic characteristics were analyzed to determine the independent predictors of the need for postoperative inotropic support.
Postoperative inotropic support was required for a parts per thousand yen12 h in 26.7% of patients. Multivariate logistic regression identified only cardiopulmonary bypass (CPB) time as an independent predictor of inotropic support (odds ratio, 1.015; 95% CI, 1.004-1.025; P = 0.004). Additional analysis was performed in the 25 patients with a CPB time of a parts per thousand yen200 min. In this analysis, only S (m) was significantly associated with the need for inotropic support for a parts per thousand yen12 h.
This study suggests that those patients who have decreased S (m) and extended CPB times are more likely to require inotropic support after surgery, independent of a preserved left ventricular EF.

File： Imai(JA, 2011).pdf

DOI： 10.1007/s00540-011-1231-3

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File： Kurokawa(A&A,2011).pdf

DOI： 10.1213/ANE.0b013e31821e9765

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To clarify the vulnerability of spinal motoneurons to excitotoxicity, we analyzed the agonal current induced by experimental ischemia in ventral lamina IX neurons of spinal cord slices from neonatal rats by using whole-cell patch-clamp. Ischemia was simulated in vitro by oxygen/glucose deprivation. Super-fusion with ischemia-simulating medium elicited an agonal inward current, which was initially slow and then became rapid. We compared 8-, 9-, 10-, 11-, and 12-day postnatal rats and found age-dependent shortening of the latency of the rapid inward current. Furthermore, the membrane capacitance (Cm) and resting membrane potential (RMP) of the lamina IX neurons demonstrated significant negative correlations with the latency of the rapid inward current. Logistic regression analysis showed that postnatal age, Cm, and RMP were independent contributing factors to ischemic vulnerability. These results suggest that not only cell volume and ionic balance but also early postnatal maturation of the intracellular environment is vital for developing vulnerability to excitotoxicity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

File： Honda(Neuroscience Letters,2011).pdf

DOI： 10.1016/j.neulet.2011.03.003

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We present a case of profound bradycardia and cardiac arrest in a 61-year-old man, which occurred during left upper lobectomy and lymph node dissection for the ligamentum arteriosum. General anesthesia was maintained by propofol TIVA combined with epidural anesthesia. During the electrocautery dissection of the lymph node of the ligamentum arteriosum the patient became extremely bradycardic for 10 min. Subsequent traction with forceps further aggravated the bradycardia leading to cardiac arrest. In order to continue the procedure, we initiated epicardial pacing and switched to isoflurane anesthesia. Given the close proximity of the lymph node of the ligamentum arteriosum to the thoracic cardiac branch of the vagus nerve and the cardiac plexus, we believe that the observed bradycardia and cardiac arrest are likely attributable to vasovagal stimulation.

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We report anesthetic management of a 6-month-old boy with Menkes disease who underwent three surgeries for vesicoureteral reflux, rupture of the bladder diverticulum, inguinal hernia, and gastroesophageal reflux. Menkes disease is a rare sex-linked disorder of copper absorption and metabolism. Anesthetic management of such patients is rather challenging because of high incidence of seizures, gastroesophageal reflux with the risk of aspiration, hypothermia, airway and vascular complications. In our patient general anesthesia was uneventfully maintained by sevoflurane combined with intravenous remifentanil and fentanyl. We experienced no major complications except some difficulties with intravenous and arterial cannulation. It was especially difficult to establish intravenous and invasive blood pressure lines because of tortuous blood vessels in this patient. We conclude that in patients with Menkes disease scheduled for surgery intravenous access should be established before the induction of general anesthesia. The necessity of invasive blood pressure monitoring should be also carefully considered beforehand.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

No groups have yet succeeded in identifying the need for re-repair of residual shunt after surgical repair of ventricular septal defect (VSD) based on quantitative evaluation of the ratio of the pulmonary blood flow to the systemic blood flow (Qp/Qs) by transesophageal echocardiography (TEE). Hence, we studied the accuracy of Qp/Qs as estimated by intraoperative TEE.
Twenty-six patients undergoing VSD closure were studied. After separation from the cardiopulmonary bypass, the presence and severity of residual leakage was evaluated by color Doppler image, and the Qp/Qs (TEE-derived Qp/Qs) was calculated by measuring the vessel diameter and the velocity-time integral of the flow profiles in the main pulmonary artery and left ventricular outflow tract. Transthoracic echocardiography (TTE) was performed at pre-discharge and at 6-12 months after the correction to confirm the presence and severity of residual leakage.
TEE detected only minor leakage, with no indication for re-repair, in 8 of the 26 patients. Nevertheless, TEE-derived Qp/Qs varied from 0.57 to 2.07 and were incorrect in 17 patients (65.4%). This meant that when TEE-derived Qp/Qs was outside the acceptable range, the patient was judged not to be in need of re-repair. TTE at pre-discharge confirmed trivial leakage in 3 patients in whom TEE had also identified similar leakages. These leakages were not observed at the follow-up TTE.
TEE-derived Qp/Qs lacks the accuracy required to play a crucial role in quantitatively measuring the severity of residual shunt, while two-dimensional TEE can reliably detect residual leakage after VSD closure and lead to optimal judgment on the need for re-repair.

File： Kurokawa(JA, 2010).pdf

DOI： 10.1007/s00540-010-0896-3

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File： Watanabe(J of clinical anesthesia,2010).pdf

DOI： 10.1016/j.jclinane.2009.09.002

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Background: The molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method.
Results: In vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist.
Conclusions: Xenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon.

File： Georgiev(Mol Pain,2010).pdf

DOI： 10.1186/1744-8069-6-25

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We report successful epidural anesthetic management in a patient with severely impaired respiratory function. A 47-year-old woman (39 kg, 158 cm) was scheduled for right thoracoplasty. She had undergone fenestration surgery for empyema three months previously and required supplemental oxygen. Her vital capacity was 700 ml and forced expiratory volume in one second was 650 ml, indicating a severe restrictive pulmonary disorder. Hence, in order to avoid general anesthesia with tracheal intubation, we opted for epidural anesthesia. An epidural catheter was inserted in the T6-7 interspace and a bolus of 4.5 ml each of 1% mepivacaine and 1% ropivacaine was injected through the epidural catheter after a test dose. Ten minutes after the injection, the patient complained of difficulty in breathing and her oxygen saturation fell from 96% to 93%. We applied noninvasive positive pressure ventilation (NPPV) via a nasal mask to the patient, with the ventilator set at spontaneous/timed mode with inspiratory/expiratory positive airway pressure of 14/5 cmH2O. With this therapy, the patient's respiratory symptoms subsided rapidly and we could maintain adequate oxygenation and ventilation throughout the operation. We believe that epidural anesthesia with NPPV is a useful option for patients with compromised respiratory function.

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47歳女。7年前両側特発性乳び胸と診断された。次第に呼吸状態悪化のため、7ヶ月前胸管結紮術を施行し、術後肺炎のため約1ヵ月人工呼吸管理を要した。3ヵ月前に難治性の膿胸に対し右胸腔開窓術を施行し、夜間の非侵襲的陽圧換気(NPPV)および労作時酸素吸入を要する状態となったが、膿胸は改善し右胸郭形成術を予定した。Hugh-Jones分類IV度で、胸部X線で左側に若干の胸水貯留と下肺野浸潤影を認めた。著しい肺機能低下のため胸部硬膜外麻酔とし、硬膜外カテーテルよりメピバカインとロピバカインの等量混合液を投与した。SpO2低下のため鼻マスクによるNPPV導入し呼吸困難は消失した。局所麻酔薬投与から15分後にT1-12の冷覚消失を確認して手術を開始した。鎮静にプロポフォールを投与し、血圧低下は輸液負荷とエフェドリン投与で対処した。手術は肋骨部分切除、肋間筋を含む周囲軟部組織の胸腔内充填を行った。閉胸時に軽度の疼痛を訴え、同じ局所麻酔薬混合液を追加投与し自発呼吸を維持して手術を遂行した。NPPV中止で酸素飽和度低下もなく、術後鎮痛にロピバカインを3日間持続硬膜外投与した。呼吸状態も良好に経過して退院した。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Potentiation of inhibitory gamma-aminobutyric acid subtype A (GABA(A)) receptor function is involved in the mechanisms of anesthetic action. The present study examined the immobilizing action of the volatile anesthetic isoflurane in mice with double knockout (DKO) of phospholipase C-related inactive protein (PRIP)-1 and -2. Both of these proteins play important roles in the expression of GABA(A) receptors containing the gamma 2 subunit on the neuronal cell surface. Immunohistochemistry for GABA(A) receptor subunits demonstrated reduced expression of gamma 2 subunits in the spinal cord of the DKO mice. Immunohistochemistry also revealed up-regulation of the alpha 1 and beta 3 subunits even though there were no apparent differences in the immunoreactivities for the beta 2 subunits between wild-type and DKO mice. The tail-clamp method was used to evaluate the anesthetic/immobilizing effect of isoflurane and the minimum alveolar concentration (MAC) was significantly lower in DKO mice compared with wild-type controls (1.07 +/- 0.01% versus 1.36 +/- 0.04% atm), indicating an increased sensitivity to isoflurane in DKO mice. These immunohistochemical and pharmacological findings suggest that reduced expression of the GABA(A) receptor gamma 2 subunit affects the composition and function of spinal GABA(A) receptors and potentiates the immobilizing action of isoflurane. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

File： Seo(Neuroscience Letters, 2010).pdf

DOI： 10.1016/j.neulet.2010.01.031

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Until recently, the N-methyl-D-aspartate (NMDA) receptor was considered to possibly mediate the immobility produced by inhaled anesthetics such as isoflurane and nitrous oxide. However, new evidence suggests that the role of this receptor in abolition of the movement response may be less important than previously thought. To provide further evidence supporting or challenging this view, we examined the anesthetic potencies of isoflurane and nitrous oxide in genetically modified animals with established NMDA receptor dysfunction caused by GluR epsilon 1 subunit knockout.
METHODS: The immobilizing properties of inhaled anesthetics in mice quantitated by the minimum alveolar anesthetic concentration (MAC) were evaluated using the classic tail clamp method.
RESULTS: Compared with wild-type controls, NMDA receptor GluR epsilon 1 subunit knockout mice displayed larger isoflurane MAC values indicating a resistance to the immobilizing action of isoflurane. Knockout mice were previously shown to have enhanced monoaminergic tone as a result of genetic manipulation, and this increase in MAC could be abolished in our experiments by pretreatment with the serotonin 5-hydroxytryptamine type 2A receptor antagonist ketanserin or with the dopamine D2 receptor antagonist droperidol at doses that did not. affect MAC values in wild-type animals. Mutant mice also displayed resistance to the isoflurane MAC-sparing effect of nitrous oxide, but this resistance was similarly abolished by ketanserin and droperidol. Thus, resistance to the immobilizing action of inhaled anesthetics in knockout mice seems to be secondary to increased monoaminergic activation after knockout rather than a direct result of impaired NMDA receptor function.
CONCLUSIONS: Our results confirm recent findings indicating no critical contribution of NMDA receptors to the immobility induced by isoflurane and nitrous oxide. In addition, they demonstrate the ability of changes secondary to genetic manipulation to affect the results obtained in global knockout studies. (Anesth Analg 2010;110:461-5)

File： Petrenko(A&A,2010).pdf

DOI： 10.1213/ANE.0b013e3181c76e73

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Intraoperative autologous blood predonation is reported to be useful for the prevention of homologous blood transfusion in cardiac operations, especially in on-pump coronary artery bypass grafting (CABG). However, CABG is now performed more often off-pump than on-pump. We analyzed the major factors of homologous blood transfusion in 25 consecutive cases of valvular heart operation with intraoperative autologous blood predonation except those with preoperative autologous blood donation. Homologous blood was not transfused in 18 cases, but was in 7 cases only after cardiopulmonary bypass (CPB). The homologous transfusion was not correlated with body weight, CPB dilution or duration, or preoperative hematocrit level, but was found to correlate with age (R 2=0.289, p=0.0413), bleeding output (R2=0.197, p=0.0485), and predonation blood volume (R2=0.436, p=0.0152). In conclusion, suitable intraoperative predonation may reduce the necessity for homologous blood transfusion in valvular heart operations. © 2010 Wichtig Editore.

DOI： 10.1177/039139881003300202

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Background: The local anesthetic bupivacaine is thought not only to block sodium channels but also to interact with various receptors. Here, the authors focus on excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord with respect to its importance for nociceptive processing.
Methods: The effects of bupivacaine on the response to exogenous administration of N-methyl-D-aspartate (NMDA) receptor agonists were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique.
Results: Bupivacaine (0.5, 2 mM) dose-dependently reduced the peak amplitudes of exogenous NMDA-induced currents. However, this inhibitory effect of bupivacaine (2 mM) was not blocked by the presence of tetrodotoxin, a sodium channel blocker, or La(3+) , a voltage-gated Ca(2+) channel blocker, and was unaffected by changes in pH conditions. Moreover. intrapipette guanosine-5&apos;-O-(2-thiodiphosphate) (1 mM), a G-protein inhibitor, did not block the reduction of NMIDA current amplitudes by bupivacaine. Similarly, lidocaine, ropivacaine, and mepivacaine also reduced the amplitudes of NMDA-induced currents.
Conclusions: These findings raise the possibility that the antinociceptive effect of bupivacaine may be due to direct modulation of NMDA receptors in the Superficial dorsal horn. In addition to voltage-gated sodium channels, glutamate NMDA receptors are also important for analgesia induced by local anesthetics.

File： Furutani(Anesthesiology,2010).pdf

DOI： 10.1097/01.anes.0000365964.97138.9a

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The analgesic effect of nitrous oxide (N(2)O) is thought to depend on noradrenaline release in the spinal cord following activation of descending inhibitory neurons. In addition to this indirect facilitation of inhibition in the spinal cord, we previously showed direct inhibition of glutamate receptors in dorsal horn neurons by N(2)O. Since general anesthetics could possibly affect excitatory and/or inhibitory components of synaptic transmission, we sought to evaluate the direct effect of N(2)O on inhibitory transmission in spinal cord neurons.
Using whole-cell patch-clamp recording from rat transversal spinal cord slices, we investigated the actions of 50% N(2)O and 0.5% isoflurane (both 0.3 rat MAC: minimum alveolar concentration) on exogenously applied gamma-aminobutyric acid (GABA)- and glycine-induced currents in rat dorsal horn lamina II neurons. The amplitudes and integrated areas of GABA- and glycine-induced currents were not significantly affected by N(2)O, but were increased in the presence of isoflurane. N(2)O did not affect the amplitude, frequency or decay time probability distribution of either GABA or glycine receptor-media red miniature postsynaptic currents. We further sought to determine the effect of N(2)O On focal stimulation-evoked synaptic Currents mediated by GABA and glycine receptors, and found no effect in the majority of neurons.
These and other findings suggest that N(2)O has a discrete action in the spinal cord, distinct from the effects of the volatile anesthetics, consisting of inhibition of excitation in SG neurons through an action on ionotropic glutamatergic receptors and potentiation of inhibition through the descending noradrenergic system. (C) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

File： Georgiev(Eur J Pain,2010).pdf

DOI： 10.1016/j.ejpain.2009.01.008

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A 7-year-old boy with congenital myotonic dystrophy (MD) and developmental retardation underwent an emergency surgery for strangulation ileus. General anesthesia was maintained using sevoflurane and fentanyl. While intraoperative arterial blood pressure, pulse and rectal temperature remained stable, the arterial blood oxygenation gradually deteriorated during the procedure. We suspected the existence of atelectasis or some other obstructive lung lesion to be the underlying cause, and performed bronchoscopic examination which revealed a collapse of the left main bronchus. Therefore, postoperative mechanical ventilation was continued for several hours in the ICU. According to the postoperative computed tomography, the left main bronchus was sandwiched between the aortic arch and thoracic vertebra. It has been reported that MD patients have a risk of perioperative pulmonary complications, particularly in those who have severe muscular disability undergoing upper abdominal surgery. These risk factors combined with bronchial stenosis could have caused intraoperative hypoxia in our patient. We conclude that when a severe MD patient is scheduled for an upper abdominal surgery, mechanical ventilation should be considered until spontaneous recovery from muscle relaxants occurs. Also, since MD has been related to malignant hyperthermia, total intravenous anesthesia, possibly combined with regional blockade, is a preferable method of anesthesia for such patients.

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A 37-year-old multigravida presented at 37 weeks of gestation with low-lying placenta and highly suspected placenta accreta. The placenta adhered widely to the anterior wall of the uterus. Therefore, a longitudinal incision of the uterine corpus at the thinnest part of the placenta was made during surgery. Concurrent with the incision, rapid and massive hemorrhage occurred. After the delivery of the baby and confirmation of the placental adhesion, the hysterectomy was started promptly. The bladder adhered strongly to the uterus, and was injured during the dissection. The total volume of hemorrhage was estimated to be 24,480 ml (including amniotic fluid and urine). No arterial clamp for hemostasis was used during the procedure. The patient was discharged on the 12th postoperative day with no sequela. The pathological diagnosis was placenta percreta. Placenta accreta is a rare disease with a high mortality rate. The hemorrhage becomes difficult to control in case of injury of placenta accreta. The hysterectomy following cesarean section also becomes complicated. Bladder injury is one of the complications of the cesarean hysterectomy which makes the hemorrhage greader. In conclusion, when placenta accreta is suspected a strategy to minimize blood loss during surgery should be discussed by a multidisciplinary team.

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：THE JAPAN SOCIETY FOR CLINICAL ANESTHESIA  

A 58-year-old woman presented with severe hypoxemia. Chest radiography showed patchy infiltrates in both lungs. A diagnosis of pulmonary alveolar proteinosis (PAP) was made. The patient needed whole-lung lavage (WLL) , and the support of extracorporeal membrane oxygenation (ECMO) was required during this procedure because of severe hypoxemia (PaO₂ 38mmHg, breathing ambient air) . We performed the ECMO-assisted left WLL without fatal hypoxemia. It is suggested that ECMO support enables PAP patients with severe hypoxemia to maintain good oxygenation during aggressive WLL and results in early patient recovery.

DOI： 10.2199/jjsca.29.829

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File： N2O(脊髄機能診断,2009）.pdf

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File： Bupivacaine(脊髄機能診断,2009）.pdf

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Background and objective: Patients who awake from sevoflurane anaesthesia with symptoms of agitation may have sonic underlying functional substrate that is sensitive to the low concentrations of anaesthetic encountered during emergence. One candidate for Such a substrate Could be neurocircuitry implied in the pathophysiology of both agitation and movement disorders with hyperactivity. We Postulated that hyperactive animals would show a further increase in activity in the presence of low concentrations of volatile anaesthetics, Such as sevoflurane. Methods: To confirm our hypothesis, we examined the effects of two subanaesthetic concentrations of sevoflurane, isoflurane and halothane (0.1, and 0.2 MAC (minimum alveolar concentration)) on spontaneous activity in N-methyl-D-aspartate receptor GluR epsilon 1 subunit knockout mice exhibiring locomotor hyperactivity in a novel environment and compared these results with those for wild-type controls. We also compared the effects of anaesthetic concentrations of sevoflurane (1.2 MAC) on mice activity during postanaesthesia recovery. Results: Out of the three anaesthetics used, only sevoflurane administered at 0.1 MAC caused a significantly different response between the two experimental groups. Exposure to this subanaesthetic concentration of sevoflurane reduced the activity of wild-type mice, whereas mutant animals showed a further increase in hyperactivity. The effects of 1.2 MAC sevoflurane anaesthesia on mice activity during postanaesthesia recovery also differed significantly between the two genotypes. Exposure to anaesthetic concentrations of sevoflurane had a sedative effect on wild-type mice, whereas Mutant mice preserved their high levels of activity upon emergence from the anaesthesia. Conclusions: The presence of an inherent anomaly in Mutant mice that becomes more manifest during exposure to 0.1 MAC sevoflurane and is still present after the emergence from sevoflurane anaesthesia Suggests the presence of and necessitates a search for some Putative substrate that may, by analogy, underlie emergence agitation in the clinical setting.

DOI： 10.1017/S0265021508004626

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Dexmedetomidine is a highly specific, potent and selective alpha(2)-adrenoceptor agonist. Although intrathecal and epidural administration of dexmedetomidine has been found to produce analgesia, whether this analgesia results from an effect on spinal cord substantia gelatinosa (SG) neurons remains unclear. Here, we investigated the effects of dexmedetomidine on postsynaptic transmission in SG neurons of rat spinal cord slices using the whole-cell patch-clamp technique. In 92% of the SG neurons examined (n = 84), bath-applied dexmedetomidine induced outward currents at -70 mV in a concentration-dependent manner, with the value of effective concentration producing a half-maximal response (0.62 mu M). The outward currents induced by dexmedetomidine were suppressed by the alpha(2)-adrenoceptor antagonist yohimbine, but not by prazosin, an alpha(1)-, alpha(2B)- and alpha(2C)-adrenoceptor antagonist. Moreover, the dexmedetomidine-induced currents were partially suppressed by the alpha(2C)-adrenoceptor antagonist JP-1302, while simultaneous application of JP-1302 and the alpha(2A)-adrenoceptor antagonist BRL44408 abolished the current completely. The action of dexmedetomidine was mimicked by the alpha(2A)-adrenoceptor agonist oxymetazoline. Plots of the current-voltage relationship revealed a reversal potential at around -86 mV. Dexmedetomidine-induced currents were blocked by the addition of GDP-beta-S [guanosine-5'-O-(2-thiodiphosphate)] or Cs+ to the pipette solution. These findings suggest that dexmedetomidine hyperpolarizes the membrane potentials of SG neurons by G-protein-mediated activation of K+ channels through alpha(2A)- and alpha(2C)-adrenoceptors. This action of dexmedetomidine might contribute, at least in part, to its antinociceptive action in the spinal cord.

DOI： 10.1111/j.1460-9568.2008.06260.x

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Taurine has been suggested to modulate nociceptive information at the spinal cord level. In this study, the pharmacological properties of taurine were investigated in adult rat substantia gelatinosa (SG) neurons using whole-cell patch-clamp method. We found that taurine seemed to have higher efficacy than glycine on glycine receptors in SG neurons. An increase in chloride conductance was responsible for taurine-induced currents. Taurine at 0.3 mM activated glycine receptors, whereas at 3 mM activated both glycine and gamma-aminobutyric acid A receptors. The currents activated by coapplication of taurine and glycine are cross inhibitive. Altogether these results show that taurine might represent another important neurotransmitter or modulator in SG neurons, which may be involved in antinociception.

File： Wu(Neuroreport,2008).pdf

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The effects of nitrous oxide (N2O) are thought to be mediated by several pharmacological pathways at different levels of the central nervous system. Here, we focus on excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord with respect to its importance for the nociceptive processing. The effects of 50% N2O on electrically evoked and spontaneous excitatory glutamatergic transmission and on the response to exogenous administration of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptor agonists were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique. Peak amplitudes of A delta- and C-fiber evoked monosynaptic NMDA- and AMPA-receptor-mediated excitatory postsynaptic currents (EPSCs) were decreased in the presence of N2O. N2O reduced the peak amplitude and integrated area of exogenous NMDA- and AMPA-induced currents. Moreover NO changed the distribution of miniature EPSC amplitude, but not frequency distribution in most neurons. N20 inhibits glutamatergic transmission in the superficial dorsal horn by modulating the NMDA- and AMPA-receptors. Our findings raise the possibility that the antinociceptive effect of N2O may be directly mediated at the level of the spinal cord. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.pain.2007.03.026

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File： シンポジウム（麻酔メカニズム2007）.pdf

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Background: T-type calcium channels regulate neuronal membrane excitability and participate in a number of physiologic and pathologic processes in the central nervous system, including sleep and epileptic activity. Volatile anesthetics inhibit native and recombinant T-type calcium channels at concentrations comparable to those required to produce anesthesia. To determine whether T-type calcium channels are involved in the mechanisms of anesthetic action, the authors examined the effects of general anesthetics in mutant mice lacking alpha(1G) T-type calcium channels.
Methods: The hypnotic effects of volatile and intravenous anesthetics administered to mutant and C57BL/6 control mice were evaluated using the behavioral endpoint of loss of righting reflex. To investigate the immobilizing effects of volatile anesthetics in mice, the minimum alveolar concentration (MAC) values were determined using the tail-clamp method.
Results: The 50% effective concentration for loss of righting reflex and MAC values for volatile anesthetics were not altered after alpha(1G) channel knockout. However, mutant mice required significantly more time to develop anesthesia/hypnosis after exposure to isoflurane, halothane, and sevoflurane and after intraperitoneal administration of pentobarbital.
Conclusions: The 50% effective concentration for loss of righting reflex and MAC values for the volatile anesthetics were not altered after alpha(1G) calcium channel knockout, indicating that normal functioning of alpha(1G) calcium channels is not required for the maintenance of anesthetic hypnosis and immobility. However, the timely induction of anesthesia/hypnosis by volatile anesthetic agents and some intravenous anesthetic agents may require the normal functioning of these channel subunits.

File： Petrenko(Anesthesiology,2007.pdf

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To investigate plastic changes in nociceptive sensitivity of the dorsal horn, slow excitatory responses elicited by iteration of high-frequency stimulation were spatiotemporally observed in spinal cord slices of young-adult rats using membrane excitation imaging techniques. Single-pulse stimulation to the dorsal root elicited membrane excitation in lamina II, and high-frequency pulse-train stimulation evoked long-lasting excitation that expanded widely in the dorsal horn. Iteration of high-frequency stimulation enhanced the strength and extent of the excitatory responses, but such augmentation of the excitatory responses disappeared in the presence of an NMDA receptor antagonist (CPP) and was hindered by an NK1 receptor antagonist (L-703.606). The results suggest that activation of both NMDA and NK1 receptors is involved in the enhancement of slow excitatory responses evoked by iteration of high-frequency stimulation. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

File： Ogawa M(Neuroscience Research,2007).pdf

DOI： 10.1016/j.neures.2006.11.011

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DOI： 10.2199/jjsca.27.332

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File： シンポジウム（麻酔メカニズム2007）.pdf

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DOI： 10.2199/jjsca.27.684

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Although the properties of ketamine appear to be well characterized, there is a lot of ambiguity in the literature regarding its analgesic effects. After careful selection of proper experimental conditions and drug doses, we systematically characterized the effects of systemic ketamine on acute somatic nociception in mice and examined the role of the NMDA receptor epsilon 1 subunit in mediating its analgesia. Intraperitoneal administration of ketamine was not analgesic in any of the phasic pain assays (thermal, mechanical, electrical) applied to C57BL/6 (wild-type) and NMDA receptor epsilon 1 subunit knockout (mutant) mice. Surprisingly, rather than being analgesic for thermal nociception, ketamine showed pronociceptive properties in case of low-intensity heat stimulation in wild-type mice. In the formalin test (tonic pain), ketamine significantly reduced phase 2 nociceptive behavior in both wild-type and mutant mice. These data indicate that in wild-type mice ketamine has no analgesic effect on phasic pain in normal somatic tissues, but alleviates tonic pain after inflammation. Such analgesic spectrum of ketamine can be fully explained by its NMDA receptor antagonist properties. The results for the mutant mice suggest that the epsilon 1 subunit of the NMDA receptor does not mediate the analgesic effects of ketamine in tonic pain. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuropharm.2005.11.019

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Background: Although intrathecal administration of midazolam, a water-soluble imidazobenzodiazepine derivative, has been found to produce analgesia, how it exerts this effect at the neuronal level in the spinal cord is not fully understood.
Methods: The effects of midazolam on electrically evoked and spontaneous excitatory transmission were examined in lamina H neurons of adult rat spinal cord slices using the whole cell patch clamp technique.
Results: Bath-applied midazolam (1 mu m) diminished A delta- and C-fiber evoked polysynaptic excitatory postsynaptic currents in both amplitude and integrated area. However, it affected neither A delta- and C-fiber evoked monosynaptic excitatory postsynaptic currents in amplitude nor miniature excitatory postsynaptic currents in amplitude, frequency, and decay time constant. In the presence of a benzodiazepine receptor antagonist, flumazenil (5 mu m), midazolam (1 mu m) did not diminish A delta-fiber evoked polysynaptic excitatory postsynaptic currents, suggesting that midazolam modulate the gamma-aminobutyric acid interneurons in the dorsal horn.
Conclusions: Midazolam reduced excitatory synaptic transmission by acting on the gamma-aminobutyric acid type A/benzodiazepine receptor in interneurons, leading to a decrease in the excitability of spinal dorsal horn neurons. This may be a possible mechanism for the antinociception by midazolam in the spinal cord.

File： Kohno(Anesthesiology,2006).pdf

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Volatile inhaled anesthetics and nitrous oxide (N2O) are often used together in clinical practice to produce analgesia. Because the analgesic effect of N2O is, at least in part, mediated by norepinephrine (NE) release in the spinal cord, we examined the interaction between isoflurane (ISO) and NE in the adult rat spinal cord with respect to central nociceptive information processing. The effects of clinically relevant concentrations of ISO (1 MAC) and NE (20 mu M) on spontaneous inhibitory transmission in substantia gelatinosa (SG) neurons were examined using the blind whole-cell patch-clamp method. ISO prolonged the decay time and increased the total charge transfer of spontaneous inhibitory postsynaptic currents. NE increased the frequency and mean amplitude of inhibitory postsynaptic currents and the charge transfer as well. Coapplication of both drugs led to an additive increase of the charge transfer and frequent temporal summation of inhibitory postsynaptic currents. We conclude that both ISO and NE enhance the inhibitory synaptic transmission in the rat SG neurons and their interaction is additive, suggesting that ISO may add to the analgesic action of N2O at the spinal cord dorsal horn level.

File： Georgiev(A&A,2006).pdf

DOI： 10.1213/01.ane.0000184829.25310

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File： Opioid(脊髄機能診断,2006).pdf

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Ketamine is an IV anesthetic and analgesic with N-methyl-d-aspartate receptor (NMDAR)-blocking properties at clinically relevant concentrations. Functional NMDARs are composed by assembly of GluRζ1 (NR1) subunit with GluRε1-4 (NR2A-D) subunits, which confer unique properties on native NMDARs. Mutant mice lacking the ε1 subunit, which is widely expressed postnatally in normal animals, were found to be resistant to ketamine-induced loss of the righting reflex (hypnosis). Surprisingly, they were also more resistant to hypnotic action of pentobarbital, which does not interact with the NMDARs at clinically relevant concentrations. These results suggest the difficulties with interpretation of altered anesthetic sensitivity in global knockouts. Although the ability of ketamine to produce somatic analgesia even at subanesthetic doses in humans is well recognized, administration of ketamine did not result in elevation of pain thresholds to thermal stimuli (phasic pain model) in wild-type and mutant mice. Ketamine dose-dependently reduced nociceptive behavior (paw licking/biting) in the second phase of the formalin test (tonic pain model) in both wild-type and mutant mice. These results argue against the contribution of the ε1 subunit to ketamine analgesia in this nociceptive assay. © 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ics.2005.07.042

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Endogenous polyamines like spermine are known to have four distinct effects on recombinant N-methyl-D-aspartate (NMDA) receptor channels: voltage-dependent inhibition, glycine-dependent Stimulation, glycine-independent stimulation and decreased affinity to the agonist (L-glutamate). These effects are highly dependent on the constituting F subunits (epsilon 1-r4) of the recombinant NMDA receptor channels. Agmatine reportedly inhibits native NMDA receptor channels in cultured hippocampal neurons. In the present investigation, the effects of agmatine on the epsilon/zeta heteromeric NMDA receptor channels expressed in Xenopus laevis oocytes were examined using the two-electrode voltage clamp method. Agmatine inhibited the four epsilon/zeta (epsilon 1/zeta 1, epsilon 2/zeta 1, epsilon 4/zeta 1 and epsilon 4/zeta 1) channels with similar sensitivity (an IC50 value of about 300 mu M at -70 mV). This effect was dependent on the membrane potential and was more pronounced at hyperpolarized membrane potentials (vottage-dependent inhibition). Agmatine did not exhibit other stimulatory (glycine-dependent and -independent effects) or inhibitory (decreased affinity to L-glutamate) effects. These properties are similar to the pharmacological profile of well-characterized NMDA receptor channel blockers like phencyclidine and ketamine. Thus, regarding the effects on the NMDA receptor channels, agmatine is not like other endogenous polyamines rather it acts as a channel blocker. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2005.05.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

The N-methyl-D-aspartate (NMDA) receptor NR3B subunit co-assembles with NR1 and NR2 subunits to form a receptor complex with distinct channel properties. In the present study, we investigated the effects of co-expression of the NR3B subunit on the anesthetic sensitivities of NMDA receptors for NR1/NR2 channels expressed in Xenopus oocytes. Although the NR3B subunit prominently reduced the current amplitude of NR1/NR2A-B channels, the sensitivities of NR1/ NR2A-B channels to Mg2+, ketamine, isoflurane, nitrous oxide, and ethanol were not altered by coexpression of the NR3B subunit. These results suggest that the anesthetic sensitivities of NMDA receptors do not depend on the presence or absence of the NR3 subunit. Mutations of two amino acid residues in the NR3B subunit at positions homologous to the N and N + 1 sites in the NR1 and NR2 subunits, which constitute the blocking sites for Mg2+ and ketamine, did not affect the sensitivities of NR1/NR2B/NR3B channels to Mg2+, ketamine and isoflurane. Thus, the amino acid residues at the N and N + 1 sites in NR3 subunits are unlikely to be involved in the formation of channel blocking sites in NR1/NR2/NR3 channels.

File： Yamakura(A&A2005).pdf

DOI： 10.1213/01.ANE.0000152324.30272.49

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Background Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immunobility and analgesia) and suppress autonomic responsiveness, how it exerts these effects at the neuronal level in the spinal cord is not fully understood.
Methods: The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the gamma-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined.
Results: Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature gamma-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity.
Conclusions: Isoflurane augments gamma-aminobutyric acid-mediated inhibitory transmission, leading to a decrease in the excitability of spinal dorsal horn neurons. This may be a possible mechanism for the antinociceptive effect of isoflurane in the spinal cord.

File： Wakai(Anesthesiology,2005).pdf

DOI： 10.1097/00000542-200502000-00021

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DOI： 10.11321/jjspc1994.12.10

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Other Link： http://search.jamas.or.jp/link/ui/2005119886

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Ketamine is an IV anesthetic with N-methyl-D-aspartate receptor (NMDAR)-blocking properties. However, it is still unclear whether ketamine's general anesthetic actions are mediated primarily via blockade of NMDAR. Functional NMDARs are composed by the assembly of a GluRzeta1 (NR1) subunit with GluRepsilon (GluRepsilon1-4; NR2A-D) subunits, which confer unique properties on native NMDARs. We hypothesized that animals deficient in GluRepsilon1, an abundant and ubiquitously postnatally expressed NMDAR subunit, might be resistant to the effects of ketamine. Here, we evaluated a righting reflex to determine the general anesthetic/hypnotic potency of ketamine administered intraperitoneally to GluRepsilon1 knockout mice and compared these results with those for wild-type mice. Mutant mice were more resistant to ketamine than control mice. Unexpectedly, mutant mice were also more resistant to pentobarbital, which is thought not to interact with NMDAR at clinically relevant concentrations. Although these data in no way eliminate the possibility of the involvement of the NMDAR GluRepsilon1 subunit in mediation of ketamine anesthesia/hypnosis, they suggest the difficulties with interpretation of altered anesthetic sensitivity in knockout animal models.

File： Petrenko(A&A,2004).pdf

DOI： 10.1213/01.ANE.0000131729

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CANADIAN ANESTHESIOLOGISTS SOC  

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Primary afferent A-fiber stimulation normally evokes fast mono- or polysynaptic EPSCs of short duration. However, in the presence of the GABA(A) receptor antagonist bicuculline, repetitive, long lasting, polysynaptic EPSCs can be observed following the initial, fast response. A-fiber-induced ERK activation is also facilitated in the presence of bicuculline. The frequency of miniature EPSCs and the amplitude of the monosynaptic A-fiber-evoked EPSCs are not affected by bicuculline or the GABA(A) receptor agonist muscimol, suggesting that GABA(A) receptors located on somatodendritic sites of excitatory interneurons are critical for this action. Bicuculline-enhanced polysynaptic EPSCs are completely eliminated by NMDA receptor antagonists APV and ketamine, as was the augmented ERK activation. This NMDA receptor-dependent phenomenon may contribute to bicuculline-induced allodynia or hyperalgesia, as well as the hypersensitivity observed in neuropathic pain patients. (C) 2003 Elsevier Inc. All rights reserved.

File： Baba & Ji(MCN,2003).pdf

DOI： 10.1016/S1044-7431(03)00236-7

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There is accumulating evidence to implicate the importance of N-methyl-D-aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, NMDA receptors may also mediate peripheral sensitization and visceral pain. NMDA receptors are,composed of NR1, NR2 (A, B, C, and D), and NR3 (A and B) subunits, which determine the functional properties of native NMDA receptors. Among NMDA receptor subtypes, the NR2B subunit-containing receptors appear particularly important for nociception, thus leading to the possibility that NR2B-selective antagonists may be useful in the treatment of chronic pain.

File： Petrenko(A&A,2003).pdf

DOI： 10.1213/01.ANE.0000081061.12235.55

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Study Design. Spinal epidural and subarachnoid spaces were observed with the newly developed fine flexible fiberscopes in 55 patients with chronic pain.
Objectives. To evaluate the fiberscopes as diagnostic tools for spinal canal disease.
Summary of Background Data. Fine flexible fiberscopes make it possible to visualize the entire length of the spinal subarachnoid space without major complications, and they may be of value for the diagnosis of certain spinal canal diseases.
Methods. The epidural and subarachnoid spaces were accessed by fine flexible fiberscopes (Purely Fine [PF] types) in the initial 45 patients and by those equipped with a tip-steering function and a working channel (Medical Science [MS] types) in the later 10 patients, respectively. The procedures were based on those of continuous epidural or subarachnoid block.
Results. Normal and abnormal subarachnoid spaces were clearly observed. When the MS types were used, the intended sites of the spinal structures could be more easily approached. In 12 patients, new diagnoses were made (chronic arachnoiditis 9, subarachnoid cyst 2, old subdural hematoma 1) that could not be found by magnetic resonance imaging or computed tomography. Additionally, chronic arachnoiditis was found in 2 patients with spinal trauma. Pathologic changes were confirmed by fiberscopic examination in 16 patients (arachnoiditis 11, spinal trauma 2, arteriovenous malformation 2, subarachnoid cyst 1). No pathologic changes could be detected in 27 patients with spinal canal stenosis, disc herniation, reflex sympathetic dystrophy, or posttraumatic pain syndrome. There were no significant differences in incidence of new diagnoses between the PF and MS types of fiberscopes. There were no major complications. There were 2 cases of light fever in the initial 10 patients and 7 cases of headache in the initial 14 patients. Only 4 cases of headache were observed in the subsequent 41 patients, in whom 20 mL of saline was injected into the epidural space.
Conclusion. These fine flexible fiberscopes may provide new diagnostic and interventional tools for spinal canal diseases, provided skilled techniques are applied.

DOI： 10.1097/01.BRS.0000083595.10862.98

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Spinal dorsal column stimulation (DCS) modulates sensory transmission, including pain, at the dorsal horn of the cord. However, the mechanisms of DCS modulatory actions and the effects of anesthetics on these mechanisms remain to be investigated. We studied the effects of isoflurane (1.0% and 2.0%) on conditioned inhibition, the amplitude decrease of the spinal cord potentials (SCPs) after a conditioning volley (DCS), in the ketamine-anesthetized rat by recording the sharp negative (N) and slow positive (P) waves of the SCPs evoked by conditioning dorsal column (DC) and testing segmental stimulations. The N wave is believed to be the synchronized activity of the dorsal horn neurons, and the P wave, primary afferent depolarization (PAD), reflecting presynaptic inhibition. The P potentials evoked by either DC or segmental stimulation were depressed by isoflurane, whereas the N waves remained unchanged, indicating that the pharmacological characteristics of these N and P waves are similar between DC-evoked and segmentally evoked SCPs. The conditioned inhibition of segmental N and P waves by DC stimulation was almost completely suppressed by 2.0% isoflurane. The conditioned inhibition of the segmental N wave was not changed by spinal cord transection, whereas the conditioned inhibition of the segmental P wave was decreased. The results indicate that isoflurane depresses presynaptic inhibition without affecting the synchronized activity of dorsal horn neurons and, most profoundly, depresses the conditioned inhibition by DC stimulation of the dorsal horn neurons and PAD. Further, the results indicate that conditioned inhibition by DC stimulation of PAD receives a facilitatory influence from the supraspinal structures, whereas that of the synchronized activity of the dorsal horn neurons does not.

File： Tobita(A&A,2003).pdf

DOI： 10.1216/01.ANE.0000068980.4025.4C

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Background and Purpose - Ischemic injury in neurons can be strongly reduced by a preceding sublethal ischemic episode, of which the mechanism is poorly understood. Although changes in the expression of apoptosis-related proteins (Bcl-2, Bcl-xl, and Bax) have been considered to be crucially important in ischemic injury, the roles these proteins play in ischemic preconditioning induced by sublethal forebrain ischemia have not been elucidated. Therefore, we investigated the transcription and expression of Bcl-2, Bcl-xl, and Bax in striatum of mice subjected to sublethal forebrain ischemia and lethal ischemia, with or without ischemic preconditioning.
Methods - Sublethal forebrain ischemia was induced in C57Black/Crj6 (C57BL/6) mice by 6 minutes of bilateral common carotid artery occlusion. The transcription and expression of Bcl- 2 family genes were detected by reverse transcription polymerase chain reaction, Western blot, and immunofluorescent staining.
Results - No detectable neuronal loss was induced in striatum by 6 minutes of bilateral common carotid artery occlusion. Transcription and expression of Bcl- 2 and Bcl-xl were increased after sublethal forebrain ischemia, which attenuated the DNA fragmentation induced by lethal ischemia. The transcription and expression of Bax remained unchanged.
Conclusions - Upregulation of Bcl- 2 and Bcl-xl but not Bax may have a role in protective ischemic preconditioning. This result indicates a potential strategy for further ischemic neuronal injury therapies.

File： Chaoran Wu,.pdf

DOI： 10.1161/01.STR.0000077255.15597.69

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Noxious afferent input following tissue damage and inflammation triggers a state of neuronal hyperexcitability-a phenomenon of central sensitization-which manifests behaviorally as allodynia and hyperalgesia. At the molecular level, maintenance of central sensitization is largely dependent on the N-methyl-D-aspartate receptor (NMDAR) activation. NMDARs are composed of GluRzeta1 (NR1) and one of four GluRepsilon (NR2) subunits, which determine the functional properties of native NMDARs. Although there is accumulating evidence to implicate. GluRepsilon2-containing NMDARs in pain mechanisms, the functional significance of GluRepsilon1-containing NMDARs in this setting has not been examined in detail. Here, we used hind paw injection of formalin, complete Freund's adjuvant and a nerve injury model to investigate the effects of GluRepsilon1 subunit gene deletion on pain-related behavior in mice. In all of the models tested, GluRepsilon1-deficient mice exhibited responses similar to wild-type controls. These results suggest that GluRepsilon1 disruption does not result in altered nociceptive behavior in mice. Although the contribution of other nociceptive pathways cannot be ruled out, we speculate that the preserved function of GluRepsilon2-containing NMDARs could explain unaltered nociceptive behavior in mutant mice. (C) 2003 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/S0168-0102(03)00061-0

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File： JP(2003).pdf

DOI： 10.1113/jphysiol.2002.036186

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：INT ASSOC STUDY PAIN (IASP) PRESS  

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File： Fiber(脊髄機能診断,2003）.pdf

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File： Isoflurane(脊髄機能診断,2003）.pdf

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File： PGE2(脊髄機能診断,2003）.pdf

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File： NA(岡本、臨床麻酔）.pdf

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Despite identification of GABA(B) receptors with gb1a-gb2 composition and the alpha2delta calcium channel subunit as putative molecular targets for gabapentin (GBP), its cellular mechanism of action has remained elusive. Therefore, we have used an in vitro spinal cord slice preparation to study the effects of GBP on lamina 11 neurons. The frequency and amplitude of spontaneous EPSCs and IPSCs were unaffected by GBP, suggesting presynaptic neurotransmitter release is not regulated. Direct modulation of postsynaptic membrane excitability is also unlikely since the level of holding current required to maintain neurons at -70, 0 and +45 mV was unaffected by GBP. Effects on excitatory and inhibitory synaptic transmission were variable across the population. Primary afferent-evoked fast glutamatergic EPSCs were unaffected by GBP, while evoked NMDA receptor-mediated EPSCs and IPSCs were variably affected. In contrast, GBP enhanced responses to bath applied NMDA in 71% of neurons. Thus, in adult rat dorsal horn, synaptic and extrasynaptic NMDA receptors may be differentially regulated by GBP perhaps due to differences in subunit composition. (C) 2002 Elsevier Science Ltd. All rights reserved.

File： Moore(Neuropharmacology).pdf

DOI： 10.1016/S0028-3908(02)00226-5

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Background: Preconditioning to ischemia is a phenomenon whereby a brief episode of sublethal ischemia and other non-lethal stressors produce protection against a subsequent detrimental ischemic insult. As mitochondrial dysfunction is related to necrotic and apoptotic neuronal death after cerebral ischemia, the authors examined if ischemic preconditioning is capable of inducing mitochondrial tolerance.
Methods: Forebrain ischemia was induced by bilateral common carotid artery occlusion with simultaneous hypotension for 8 min in Wistar rats (275-300 g). A 3-min ischemic episode performed 48 It before the 8-min ischemia was used for preconditioning. The extents of hippocampal CA1 neuronal damage were evaluated 7 days after reperfusion by neuro-specific nuclear protein immunostaining. Brain mitochondria were isolated 48 It after animals were subjected to the sham operation or the 3-min conditioning ischemia. Loss of cytochrome c from mitochondria after cerebral ischemia in vivo and after exposure of brain mitochondria to calcium in vitro was used as an indication of mitochondrial dysfunction.
Results: Results showed that ischemic preconditioning induced by a 3-min ischemic episode dramatically reduced the loss of hippocampal CA1 neurons resulting from a subsequent 8-min ischemia 7 days after reperfusion, and this protection was associated with a preservation of mitochondrial cytochrome c as examined after early reperfusion. Exposure of isolated brain mitochondria to calcium produced a dose-dependent increase in cytochrome c release either at 30degreesC or at 37degreesC. Compared with those animals receiving only sham operation, cytochrome c release caused by 100 muM calcium was significantly reduced in conditioned animals.
Conclusion: Regarding the importance of mitochondrial dysfunction in mediating ischemic neuronal death, the above results indicate that mitochondria may serve as end-effecting organelles to ischemic preconditioning.

File： Zhan(Anesthesiology,2002),.pdf

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File： Ishii(A&A,2002).pdf

DOI： 10.1213/01.ANE.000019029.7747.C2

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To clarify whether inhibitory transmission in the superficial dorsal horn of the spinal cord is reduced after peripheral nerve injury, we have studied synaptic transmission in lamina II neurons of an isolated adult rat spinal cord slice preparation after complete sciatic nerve transection (SNT), chronic constriction injury (CCI), or spared nerve injury (SNI). Fast excitatory transmission remains intact after all three types of nerve injury. In contrast, primary afferent-evoked IPSCs are substantially reduced in incidence, magnitude, and duration after the two partial nerve injuries, CCI and SNI, but not SNT. Pharmacologically isolated GABA(A) receptor-mediated IPSCs are decreased in the two partial nerve injury models compared with naive animals. An analysis of unitary IPSCs suggests that presynaptic GABA release is reduced after CCI and SNI. Partial nerve injury also decreases dorsal horn levels of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) 65 kDa ipsilateral to the injury and induces neuronal apoptosis, detected by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining in identified neurons. Both of these mechanisms could reduce presynaptic GABA levels and promote a functional loss of GABAergic transmission in the superficial dorsal horn.

File： Moore (JNS).pdf

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

Although the function of somatodendritic GABAA receptors is augmented by propofol, it is not known whether presynaptic GABAA receptor function is similarly affected. In the present study, we examined the action of propofol on the second positive wave (P2 component) of segmental spinal cord evoked potentials (seg SCEPs), which is believed to reflect GABAA receptor-mediated presynaptic inhibition of primary afferent terminals and can be recorded from spinal epidural space in man. In all seven patients tested while undergoing scoliosis surgery, a clinical dose of propofol (1 mg/kg, i.v.) significantly augmented the P2 component of seg SCEPs evoked by ulner nerve stimulation. We conclude that propofol enhances GABAA receptor-mediated presynaptic inhibition at primary afferent terminals in human spinal cord. © 2002 Lippincott Williams &amp
Wilkins.

DOI： 10.1097/00001756-200203040-00021

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Caspase-3 activation has been implicated in ischemic neuronal death. In the present study, we examined if cerebral ischemic tolerance induced by sublethal ischemia is associated with an attenuation of caspase-3 activation in a mouse forebrain ischemia model. Forebrain ischemia in C57Black/Crj6 strain mice was induced by bilateral common carotid artery occlusion (BCCAO) for 18 min. Two episodes of 6-min ischemia were carried out as preconditioning 48 and 72 h before the 18-min BCCAO. Caspase-3-like activity was determined by fluorescently monitoring the release of amino-4-methylcoumarin from N-acetyl-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin in the striatal protein extracts at 4, 24, and 72 h after reperfusion. The results showed that the ischemic preconditioning significantly attenuated caspase-3 activation at 4, 24, and 72 h after reperfusion, and reduced neuronal loss caused by the 18-min ischemia as examined on the 7th day after reperfusion. The present results suggest that the neuroprotection achieved by ischemic preconditioning is related to an attenuation of caspase-3 activation. (C) 2001 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0304-3940(01)02368-0

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More accurate segmental and sagittal positioning of the epidural catheter tip is required for the success of continuous epidural analgesia, spinal cord monitoring, and percutaneous epidural spinal cord stimulation. We examined the usefulness of an electrical stimulation test for verifying the proper placement of the epidural catheter tip at the predicted site in the posterior epidural space by using a locally developed epidural catheter with electrodes at its tip. The test included the observation of segmental bilateral muscle twitches and the patient's report of feeling in the region stimulated by moving the epidural catheter electrode back and forth and changing the direction of the bevel of the Tuohy needle. The success rate of midline placement at the required spinal segment was significantly more frequent (99%; P &lt; 0.001) in the group (n = 289) receiving the electrical stimulation test compared with the group (n = 277) not receiving the test (success rate 57%). The results indicate the usefulness of this method. We concluded that the electrical stimulation test is effective for verifying the proper placement of the catheter electrode tip.

File： Hayatsu(A&A,2001).pdf

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Cutaneous sensory neurons that detect noxious stimuli project to the dorsal horn of the spinal cord, while those innervating muscle stretch receptors project to the ventral horn. DRG11, a paired homeodomain transcription factor, is expressed in both the developing dorsal horn and in sensory neurons, but not in the ventral spinal cord. Mouse embryos deficient in DRG11 display abnormalities in the spatio-temporal patterning of cutaneous sensory afferent fiber projections to the dorsal, but not the ventral spinal cord, as well as defects in dorsal horn morphogenesis. These early developmental abnormalities lead, in adults, to significantly attenuated sensitivity to noxious stimuli. In contrast, locomotion and sensori-motor functions appear normal. Drg11 is thus required for the formation of spatio-temporally appropriate projections from nociceptive sensory neurons to their central targets in the dorsal horn of the spinal cord.

File： Chen(Neuron).pdf

DOI： 10.1016/S0896-6273(01)00341-5

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1. Functional reorganization of sensory pathways in the rat spinal dorsal horn following sciatic nerve transection was examined using spinal cord slices with an attached dorsal root. Slices were obtained from animals whose sciatic nerve had been transected 2-4 weeks previously and compared to sham-operated controls.
2. Whole-cell recordings from substantia gelatinosa neurones in sham-operated rats, to which nociceptive information was preferentially transmitted, revealed that dorsal root stimulation sufficient to activate A delta afferent fibres evoked a mono- and/or polysynaptic EPSC in 111 of 131 (similar to 85%) neurones. This is in contrast to the response following A beta fibre stimulation? where monosynaptic EPSCs were observed in 2 of 131 (similar to2%) neurones and polysynaptic EPSCs were observed in 18 of 131 (similar to 14%) neurones.
3. In sciatic nerve-transected rats, however, a polysynaptic EPSC following stimulation of A beta afferents was elicited in 30 of 37 (81%) neurones and a monosynaptic EPSC evoked by A beta afferent stimulation was detected in a subset of neurones (4 of 37, similar to 11%).
4. These observations suggest that, following sciatic nerve transection, large myelinated A beta afferent fibres establish synaptic contact with interneurones and transmit innocuous information to substantia gelatinosa. This functional reorganization of the sensory circuitry may constitute an underlying mechanism, at least in part, for sensory abnormalities following peripheral nerve injuries.

File： Okamoto(JP,2001).pdf

DOI： 10.1111/j.1469-7793.2001.0241g.x

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SOC NEUROSCIENCE  

Whole-cell patch-clamp and intracellular recording techniques have been used to study the action of prostaglandin E2 (PGE2) on neurons in adult rat transverse spinal cord slices. Bath-applied PGE2 (1-20 muM) induced an inward current or membrane depolarization in the majority of deep dorsal horn neurons (laminas III-VI; 83 of 139 cells), but only in a minority of lamina II neurons (6 of 53 cells). PGE2 alone never elicited spontaneous action potentials; however, it did convert subthreshold EPSPs to suprathreshold, leading to action potential generation. PGE2-induced inward currents were unaffected by perfusion with either a Ca2+-free/high Mg2+ (5 mM) solution or tetrodotoxin (1 muM), indicating a direct postsynaptic action. Both 17-phenyl trinor prostaglandin E2 (an EP1 agonist) and sulprostone (an EP3 agonist) had little effect on membrane current, whereas butaprost methyl ester (an EP2 agonist) mimicked the effect of PGE2. Depolarizing responses to PGE2 were associated with a decrease in input resistance, and the amplitude of inward current was decreased as the holding potential was depolarized. PGE2-induced inward currents were reduced by substitution of extracellular Na+ with N-methyl-D-glucamine and inhibited by flufenamic acid (50-200 muM), which is compatible with activation of a nonselective cation channel. These results suggest that PGE2, acting via an EP2-like receptor, directly depolarizes spinal neurons. Moreover, these findings imply an involvement of spinal cord-generated prostanoids in modulating sensory processing through an alteration in dorsal horn neuronal excitability.

File： Baba(PGE2,JNS,2001).pdf

DOI： 10.1523/JNEUROSCI.21-05-01750.2001

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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Background: Morphine and ketamine may prevent central sensitization during surgery and result in preemptive analgesia. The reliability of preemptive analgesia, however, is controversial.
Methods: Gastrectomy patients were given preemptive analgesia consisting of epidural morphine, intravenous low-dose ketamine, and combinations of these in a randomized, double-blind manner. Postsurgical pain intensity was rated by a visual analog scale, a categoric pain evaluation, and cumulative morphine consumption.
Results: Preemptive analgesia by epidural morphine and by Intravenous low-dose ketamine were significantly effective but not definitive. With epidural morphine, a significant reduction in visual analog scale scores at rest was observed at 24 and 48 h, and morphine consumption was significantly lower at 6 and It h, compared with control values. With intravenous ketamine, visual analog scale scores at rest and morphine consumption were significantly lower at 6, 12, 24, and 48 h than those in control subjects. The combination of epidural morphine and intravenous ketamine provided definitive preemptive analgesia: Visual analog scale scores at rest and morphine consumption were significantly the lowest at 6, 12, 24, and 48 h, and the visual analog scale score during movement and the categoric pain score also were significantly the lowest among the groups.
Conclusion: The results suggest that for definitive preemptive analgesia, blockade of opioid and N-methyl-D-aspartate receptors is necessary for upper abdominal surgery such as gastrectomy; singly, either treatment provided significant, but not definitive, postsurgical pain relief. Epidural morphine may affect the spinal cord segmentally, whereas intravenous ketamine may block brain stem sensitization ain the vagus nerve during upper abdominal surgery.

File： Aida(Anesthesiology,2000).pdf

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Background: The activation of descending norepinephrine containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha(2) receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa.
Methods: Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated.
Results: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 mu M) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)-ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected, This augmentation was mimicked by an alpha(1)-receptor agonist, phenylephrine (10-60 mu M), and inhibited by alpha(1)-receptor antagonists prazosin (0.5 mu M) and 2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane (0.5 mu M). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine.
Conclusion: These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha(1) receptors, thus providing a mechanism underlying the clinical use of of, agonists with local anesthetics in spinal anesthesia.

File： NApart1(Anesthesiology2000).pdf

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Background: It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons, in the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are ''GABAergic.''
Methods: A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied.
Results: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 mu M) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents, These increases were blocked by tetrodotoxin (1 mu M). The effects of norepinephrine mere mimicked by the alpha(1)-receptor agonist phenylephrine (10-80 mu M) and inhibited by the alpha(1)-receptor antagonist WB-4101 (0.5 mu M). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 mu M).
Conclusion: The observations suggest that GABAergic interneurons possess somatodendritic alpha(1) receptors, and activation of these receptors excites inhibitory interneurons, The alpha(1) actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine.

File： NApart2(Anesthesiology2000).pdf

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Background: Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord.
Methods: The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique.
Results: Bath-applied midazolam (1 mu M) prolonged the decay phase of evoked and miniature Inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 mu M) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 mu M); glycine currents were, however, unaltered by midazolam.
Conclusions: Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.

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Silent NMDA receptor-mediated synapses are developmentally regulated in the dorsal horn of the rat spinal cord. J. Neurophysiol. 83: 955-962, 2000. In vitro whole cell patch-clamp recording techniques were utilized to study silent pure-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic responses in lamina II (substantia gelatinosa, SG) and lamina III of the spinal dorsal hem. To clarify whether these synapses are present in the adult and contribute to neuropathic pain, transverse lumbar spinal cord slices were prepared from neonatal, naive adult and adult sciatic nerve transected rats. In neonatal rats, pure-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) were elicited in SG neurons either by focal intraspinal stimulation (n = 15 of 20 neurons) or focal stimulation of the dorsal root (n = 2 of 7 neurons). In contrast, in slices from naive adult rats, no silent pure-NMDA EPSCs were recorded in SG neurons following focal intraspinal stimulation (n = 27), and only one pure-NMDA EPSC was observed in lamina III (n = 23). Furthermore, in rats with chronic sciatic nerve transection, pure-NMDA EPSCs were elicited by focal intraspinal stimulation in only 2 of 45 SG neurons. Although a large increase in A beta fiber evoked mixed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptor-mediated synapses was detected after sciatic nerve injury, A beta fiber-mediated pure-NMDA EPSCs were not evoked in SG neurons by dorsal root stimulation. Pure-NMDA receptor-mediated EPSCs are therefore a transient, developmentally regulated phenomenon, and, although they may have a role in synaptic refinement in the immature dorsal horn, they are unlikely to be involved in receptive field plasticity in the adult.

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File： Kohno(Anesthesiology,2000).pdf

DOI： 10.1097/00000542-200602000-00020

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File： Ji RR,Nature Neurosci(1999).pdf

DOI： 10.1038/16040

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Other Link： http://www.nature.com/articles/nn1299_1114

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE AMERICA INC  

We investigated the involvement of extracellular signal-regulated protein kinases (ERK) within spinal neurons in producing pain hypersensitivity. Within a minute of an intense noxious peripheral or C-fiber electrical stimulus, many phosphoERK-positive neurons were observed, most predominantly in lamina I and IIo of the ipsilateral dorsal horn. This staining was intensity and NMDA receptor dependent. Low-intensity stimuli or A-fiber input had no effect. Inhibition of ERK phosphorylation by a MEK inhibitor reduced the second phase of formalin-induced pain behavior, a measure of spinal neuron sensitization. ERK signaling within the spinal cord is therefore involved in generating pain hypersensitivity. Because of its rapid activation, this effect probably involves regulation of neuronal excitability without changes in transcription.

File： Ji RR,Nature Neurosci(1999).pdf

DOI： 10.1038/16040

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The reliability of preemptive analgesia is controversial. Its effectiveness may vary among anatomical areas or surgical types. We evaluated preemptive analgesia by epidural morphine in six surgery types in a randomized, double-blind manner. Pain intensity was rated using a visual analog scale, a verbal report, and a measurement of postsurgical morphine consumption. Preemptive analgesia was effective in limb surgery and mastectomy, but ineffective for gastrectomy, hysterectomy, hemiorrhaphy, and appendectomy. Relief of postsurgical pain in hemiorrhaphy was more rapid than that in the other surgery types. Preemptive analgesia was effective in Limb surgery and mastectomy, but not in surgeries involving laparotomy, regardless of whether the surgery was major (gastrectomy and hysterectomy) or minor (herniorrhaphy and appendectomy). These results suggest that viscero-peritoneal nociception is involved in postsurgical pain. The abdominal viscera and peritoneum are innervated both heterosegmentally tin duplicate or triplicate by the vagus and/or phrenic nerves) and segmentally Coy the spinal nerves). Therefore, supraspinal and/or cervical spinal neurons might be sensitized, despite the blockade of the segmental nerves with epidural morphine. The rapid retreat of the pain after hemiorrhaphy suggests that central sensitization remits soon after minor surgery, but that in appendicitis, it may be protracted by additional noxious stimuli, such as infection. Implications: Epidural preemptive analgesia was reliably effective in limb and breast surgeries but ineffective in abdominal surgery, suggesting involvement of the brainstem and cervical spinal cord via the vagous and phlenic nerves.

File： Aida(A&A,1999).pdf

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Whole-cell patch-clamp recordings were made from substantia gelatinosa (SG) neurons in thick adult rat transverse spinal cord slices with attached dorsal roots to study changes in fast synaptic transmission induced by peripheral inflammation. In slices from naive rats, primary afferent stimulation at Ap fiber intensity elicited potysynaptic EPSCs in only 14 of 57 (25%) SG neurons. In contrast, A beta fiber stimulation evoked polysynaptic EPSCs in 39 of 62 (63%) SG neurons recorded in slices from rats inflamed by an intraplantar injection of complete Freund's adjuvant (CFA) 48 hr earlier (p &lt; 0.001). Although the peripheral inflammation had no significant effect on the threshold and conduction velocities of A beta, A delta, and C fibers recorded in dorsal roots, the mean threshold intensity for eliciting EPSCs was significantly lower in cells recorded from rats with inflammation (naive: 33.2 +/- 15.1 mu A, n = 57; inflamed: 22.8 +/- 11.3 mu A, n = 62, p &lt; 0.001), and the mean latency of EPSCs elicited by AP fiber stimulation in CFA-treated rats was significantly shorter than that recorded from naive rats (3.3 +/- 1.3 msec, n = 36 vs 6.0 +/- 3.5 msec, n = 12; p = 0.010). AP fiber stimulation evoked polysynaptic IPSCs in 4 of 25 (16%) cells recorded from naive rat preparations and 14 of 26 (54%) SG neurons from CFA-treated rats (p &lt; 0.001). The mean threshold intensity for IPSCs was also significantly lower in CFA-treated rats (naive: 32.5 +/- 15.7 mu A, n = 25; inflamed: 21.9 +/- 9.9 mu A, n = 26, p = 0.013). The facilitation of AP fiber-mediated input into the substantia gelatinosa after peripheral inflammation may contribute to altered sensory processing.

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1. Blind patch clamp recordings were made from substantia gelatinosa (SG) neurones in the adult rat spinal cord slice to study the mechanisms of cholinergic modulation of GABAergic inhibition.
2. In the majority of SG neurones tested, carbachol (10 mu M) increased the frequency (677 % of control) of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs). A portion of these events appeared to result from the generation of spikes by GABAergic interneurones, since large amplitude IPSCs were eliminated by tetrodotoxin (1 mu M).
3. The effect of carbachol on spontaneous IPSCs was mimicked by neostigmine, suggesting that GABAergic interneurones are under tonic regulation by cholinergic systems.
4. The frequency of GABAergic miniature IPSCs in the presence of tetrodotoxin (1 mu M) was also increased by carbachol without affecting amplitude distribution, indicating that acetylcholine facilitates quantal release of GABA through presynaptic mechanisms
5. Neither the M-1 receptor agonist McN-A-343 (10-300 mu M) nor the M-2 receptor agonist, arecaidine (10-100 mu M), mimicked the effects of carbachol. All effects of carbachol and neostigmine were antagonized by atropine (1 mu M), while pirenzepine (100 nM), methoctramine (1 mu M) and hexahydrosiladifenidol hydrochloride, p-fluoro-analog (100 nM) had no effect.
6. Focal stimulation of deep dorsal horn, but not dorsolateral funiculus, evoked a similar increase in IPSC frequency to that evoked by carbachol, and neostigmine. The stimulation induced facilitation of GABAergic transmission lasted for 2-3 min post stimulation, and the effect was antagonized by atropine (100 nM).
7. Our observations suggest that GABAergic interneurones possess muscarinic receptors on both axon terminals and somatodendritic sites, that the activation of these receptors increases the excitability of inhibitory interneurones and enhances GABA release in SG and that the GABAergic inhibitory system is further controlled by cholinergic neurones located in the deep dorsal horn. Those effects may be responsible for the antinociceptive action produced by the intrathecal administration of muscarinic agonists and acetylcholinesterase inhibitors.

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Minor brain injury was inflicted with a small hypodermic needle at four sites from the scalp 7 days before the production of convulsion by i.p. injection of 100 mg/kg lidocaine in mice. The latency to convulsion and survival rate were significantly longer and higher, respectively, in the brain-injured group than in the sham-operated one. Thus, the results suggest that a protective mechanism develops in the injured brain against asphyxia caused by lidocaine convulsion. (C) 1997 Elsevier Science B.V.

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Opioid supplements are often required in total intravenous anesthesia (TIVA). Most κ-opiate receptors are found in the spinal cord, whereas μ-opiate receptors are widespread throughout the brain and spinal cord. Buprenorphine has a strong μ-action with a minute κ-action, while eptazocine stimulates κ-receptors only. From these, epidural eptazocine is expected to exert strong spinal analgesia by κ-stimulation without μ-action, which produces circulatory and respiratory depression. Therefore, the clinical effects of epidural opioids on circulation, respiration, and analgesia were compared. Continuous epidural administration of eptazocine or buprenorphine was combined with TIVA in patients scheduled for elective abdominal surgery. Epidural opioid administration was continued throughout and for 72 h after anesthesia. A significant analgesic effect (P &lt
0.01) of epidural eptazocine without circulatory and respiratory depression was observed. With epidural buprenorphine, circulatory and respiratory depression during and immediately after anesthesia were significant (P &lt
0.05). These results suggest that medullary μ-stimulation by an epidural opioid induces circulatory (hypervagotonicity and hypervagosensitivity) and respiratory depression, while κ-stimulation produces only minimal effects on circulatory and respiratory systems.

DOI： 10.1007/BF02480068

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File： Pain Research(1997)圧縮.pdf

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Somatosensory evoked potentials (ppSEPs) in response to stimulation of the median nerve at the wrist and the cauda equina at the epidural space (the L4 level) were recorded from the posterior wall of the pharynx in 15 patients who underwent spinal surgery under general anesthesia, using disc electrodes attached to the endotracheal tube, and compared with segmental spinal cord potentials (seg-SCPs) that were recorded simultaneously from the posterior epidural space (PES). ppSEPs consisted of the initially positive spike (P9) followed by slow positive (P13) and negative (N22) waves. The P13 and N22 of ppSEPs had phase reversal relationship with the P2 and N2 recorded from the PES, respectively. The peak latencies of P9 (9.40 +/- 0.7 ms) (mean +/- SD), P13 (13.1 +/- 0.9 ms), and N22 (22.0 +/- 2.1 ms) of ppSEPs coincided with those of P1, N1 and P2 of seg-SCPs, respectively. ppSEPs were recorded more clearly with a reference electrode on the dorsal surface of the neck than with the reference electrode at the earlobe or back of the hand. The threshold and maximal stimulus intensities were also similar between the ppSEPs and seg-SCPs. Thus, the P9, P13, and N22 components of ppSEPs were thought to have the same origin as the P1, N1 and P2 of seg-SCPs, respectively. Therefore, the P9, P13 and N22 of ppSEPs may reflect incoming volleys through the root, synchronized activities of the interneurons and primary afferent depolarizations (PAD), respectively. ppSEPs in response to cauda equina stimulation showed that the latencies of the two initial components (4.6 +/- 0.4 and 6.4 +/- 0.6 ms) corresponded to those of the SCPs recorded from the PES (4.6 +/- 0.3 and 6.3 +/- 0.5 ms), suggesting that these potentials reflect impulses conducting through the spinal cord, similar to epidurally recorded SCPs.

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It has been suggested that heterosegmentally activated slow positive potentials (HSP), recorded from the spinal cord of rat and humans, are feedback inhibitory potentials. The present study was carried out to define ascending and descending spinal tracts and the sites of central nuclei involved in the production of these HSP, and the effects of ketamine on these central nuclei. The spinal cords in ketamine-anaesthetized rats were transected to determine the ascending and descending tracts involved in the production of hindpaw (HP) and forepaw (FP) HSP, respectively. Lesions of the brain at various levels were performed stereotactically during ketamine anaesthesia. Dorsal one-third resection of the cord at the T8-9 level did not affect HSP significantly, while contralateral lesion of the dorsal two-thirds of the cord decreased FP-HSP but not HP-HSP during ketamine. Bilateral transection of the ventral one-third of the cord abolished both HSP. Ablation of the cerebral cortex, cerebellum, thalamus, midbrain and pens did not affect HSP significantly. However, transection of the middle medulla decreased, while transection of the most caudal part of the medulla completely abolished both HSP. Ketamine decreased HSP even in the medulla-spinal cord preparation and the segmental slow positive wave in spinalized animals. In ketamine-anaesthetized rats, ascending and descending spinal tracts involved in the production of HP-HSP and FP-HSP are located bilaterally in the ventrolateral quadrant and in the contralateral lateral funiculus and ventrolateral quadrant, respectively. Principal central nuclei feeding back HSP might be situated diffusely in the medulla down to the caudal part. Ketamine is suggested to suppress these inhibitory feedback potentials predominantly at, and partly even below, the level of the medulla.

File： Denda(BJA,1996).pdf

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Slow negative (N) and slow positive (P) waves are frequently produced in the posterior epidural space at the lumbosacral enlargement by epidural stimulation of the rostral part of human spinal cord. The production of these slow potentials are thought to be responsible for analgesia at the stimulated segment as well as below that level. In order to define the spinal tract which mediates these slow potentials, we stimulated directly or from the epidural space the dorsal, dorsolateral, lateral and ventral columns at the cervical or thoracic level, and epidurally recorded spinal cord potentials (des.SCPs) at the lumbosacral enlargement in 7 patients who underwent spine or spinal cord surgery. The des.SCPs recorded in the lumbosacral enlargement consisted of polyphasic spike potentials followed by slow N and P waves. At a near threshold level of stimulus intensity the slow N and P potentials were consistently elicited only by stimulation of the dorsal column. The slow waves were also produced by intense stimulation of other tracts, bur remained significantly (P &lt; 0.05-P &lt; 0.01) smaller than those evoked by dorsal column stimulation when compared at the same stimulus intensity. Moreover, the slow P wave could not be elicited even by intense stimulation (10 times the threshold strength for the initial spike potentials) of the ventral column. Thus, the results suggest that the slow N and P waves are mostly mediated by the antidromic impulses descending through the dorsal column.

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To address the question of whether fine myelinated and unmyelinated primary afferent fibers contribute to the mechanism of presynaptic inhibition in the spinal cord, we studied dorsal root-evoked dorsal root potentials (DR-DRPs) using a newly developed longitudinal spinal cord slice preparations in the adult rat. single stimuli applied to the L6 dorsal root elicited a DR-DRP in the L5 dorsal root which had an amplitude of 50-150 mu V and had a half decay time of 20-66 ms. The DR-DRP was depressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-20 mu M), while DL-2-amino-5-phosphonovaleric acid (APV, 50-100 mu M) had no significant effect. DR-DRP was markedly depressed by bicuculline or picrotoxin. The evoked DR-DRP was unchanged in rats treated with capsaicin which eliminated the majority of unmyelinated C afferent fibers. Taken together with the higher voltages (greater than or equal to 1.9 V) required to elicit DR-DRP, this observation strongly suggests that the A delta afferent fibers are primarily responsible for producing and receiving the DR-DRP. The present study shows that the DR-DRP mediated by the A delta fibers in the slice preparation is analogous to those described for larger myelinated fibers in vivo. This pathway may contribute importantly to synaptic modulation of somatosensory information, including nociception at the superficial dorsal horn through an interneuronal connection which are mediated by the non-NMDA and GABA(A) receptors.

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Language：Japanese   Publisher：JAPANESE ASSOCIATION FOR STUDY OF PAIN  

DOI： 10.11154/pain.10.51

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：RESEARCH GROUP ANESTHETIC MECHANISM JAPAN  

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DOI： 10.1007/BF02514635

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For monitoring spinal cord functions during corrective surgery of scoliosis, we have recorded percutaneously from the posterior extradural space at the C5-7 levels the ascending conducted spinal cord potentials (ASCP) in response to extradural stimulation of the cauda equina in 134 patients. The ASCP consists of three spike-like components (C1, C2 and C3) followed by slow components. The extradurally recorded ASCP were not affected by anaesthetic agents. There were no significant differential effects of spinal distractions on each of the three spike potentials. There were no postoperative neurological abnormalities in patients whose ASCP showed no changes, amplitude increases, amplitude decreases of less than 50% or latency increases (&gt; 0.2 ms) during spinal manipulations (no false negatives, but some false positives). Five patients who suffered postoperative neurological damage exhibited more than 50% changes in amplitude of the ASCP during surgery. All these neurological sequelae occurred in the first 80 patients. In the last 54 patients, in whom the distraction forces on the spine were controlled rapidly by observation of the amplitude changes in ASCP, there were no postoperative neurological abnormalities, except for one patient in whom an accidental spinal cord injury was produced by a hook. The results suggest that the distraction force on the spine must be reduced immediately when the amplitudes of the ASCP decrease by more than 50% of control values with or without latency increases.

File： Fujioka(BJA,1994).pdf

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1. To study the mechanism of dorsal column stimulation-induced depression of nociceptive transmission in the spinal cord, synaptic responses evoked in dorsal horn neurones by dorsal column and dorsal root stimulations were examined in a horizontal spinal cord slice of the adult rat. Intracellular recordings were made from substantia gelatinosa (SG) neurones.
2. All SG neurones examined received monosynaptic inputs and/or polysynaptic inputs from both dorsal column and dorsal root. AS fibres were probably responsible for the synaptic responses. The responses evoked by dorsal column stimulation were similar to those evoked by primary afferent AS fibre stimulation.
3. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by dorsal column AS fibres were depressed by 8-cyano-7-nitroquinoxaline-2,3-dione, suggesting that these fibres released L-glutamate or a related amino acid as a transmitter.
4. In 38 of 101 SG neurones, dorsal column stimulation evoked an initial EPSP followed by fast and/or slow inhibitory postsynaptic potentials (IPSPs). These IPSPs reversed polarity at a membrane potential of -73 +/- 2 mV. The fast IPSPs observed in 16 of the SG neurones (42 %) that received inhibitory inputs were depressed by strychnine, while the slow IPSPs observed in 22 SG neurones were depressed by bicuculline. In a few cells, a long-lasting slow IPSP with a much slower time course was detected; this IPSP was insensitive to strychnine and bicuculline, and reversed polarity at a membrane potential near -90 mV.
5. Repetitive stimulation of the dorsal column depressed the amplitude of monosynaptic EPSPs evoked by dorsal root stimulation.
6. The responses of SG neurones to dorsal column stimulation had configurations and durations similar to responses to dorsal root stimulation, and may be mediated largely by the same AS fibres. However, a C fibre-mediated response could not be detected in SG neurones from dorsal column stimulation, although dorsal root stimulation could evoke C fibre-mediated monosynaptic EPSPs in 18 of 88 SG neurones (20 %).
7. These observations suggest that XG neurones receive abundant A delta but not C fibre inputs from the dorsal column and that dorsal column stimulation inhibits primary afferent transmission in the spinal cord both by reducing transmitter release from primary AS fibres and by hyperpolarizing SQ neurones.

File： jphysiol00345-0089.pdf

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Evoked spinal cord potentials (SCPs) were recorded from the posterior epidural space (PES) at the cervical and lumbrosacral enlargements in response to electrical stimulation of the brachial plexus at Erb's point in 17 chronic pain patients. Erb's point stimulation produced slow positive potentials (heterosegmental slow positive potentials, HSPs) in the PES at the lumbrosacral enlargement in all 13 subjects without spinal cord lesions but not in 4 subjects with spinal cord lesions. The HSP1 with a central peak latency of 21 +/- 2 ms (mean +/- SE) was recorded at the stimulus intensity up to two to three times the threshold strength (T) of the initially positive spike (P1) of the segmental SCP, which was simultaneously recorded from the PES at the cervical enlargement At the stimulus intensity of more than 3T, another slow positive potential (HSP2) with central peak latency of 71 +/- 6 ms was recorded. These slow positive potentials (HSP1 and HSP2) might be produced by a feedback loop via supraspinal structures, presumably primary afferent depolarizations, in comparison to the HSPs of our previous studies in the rat. Slow negative potentials were sometimes noted before (5 of 13) and/or after (2 of 13) the HSP1. These slow negative potentials probably reflect the activities of dorsal horn neurons producing the HSP1 and HSP2, respectively, also elicited by a feedback loop via supraspinal structures.

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：KLUWER ACADEMIC PUBL  

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Language：Japanese   Publisher：日本外科代謝栄養学会  

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Language：Japanese   Publisher：(一社)日本運動器疼痛学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

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Other Link： http://hdl.handle.net/10191/35333

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Other Link： http://search.jamas.or.jp/link/ui/2012211811

Language：Japanese   Publisher：真興交易(株)医書出版部  

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Taurine has been suggested to modulate nociceptive information at the spinal cord level. In this study, the pharmacological properties of taurine were investigated in adult rat substantia gelatinosa (SG) neurons using whole-cell patch-clamp method. We found that taurine seemed to have higher efficacy than glycine on glycine receptors in SG neurons. An increase in chloride conductance was responsible for taurine-induced currents. Taurine at 0.3 mM activated glycine receptors, whereas at 3 mM activated both glycine and gamma-aminobutyric acid A receptors. The currents activated by coapplication of taurine and glycine are cross inhibitive. Altogether these results show that taurine might represent another important neurotransmitter or modulator in SG neurons, which may be involved in antinociception.

DOI： 10.1097/WNR.0b013e3282f50c90

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

The effects of nitrous oxide (N2O) are thought to be mediated by several pharmacological pathways at different levels of the central nervous system. Here, we focus on excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord with respect to its importance for the nociceptive processing. The effects of 50% N2O on electrically evoked and spontaneous excitatory glutamatergic transmission and on the response to exogenous administration of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptor agonists were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique. Peak amplitudes of A delta- and C-fiber evoked monosynaptic NMDA- and AMPA-receptor-mediated excitatory postsynaptic currents (EPSCs) were decreased in the presence of N2O. N2O reduced the peak amplitude and integrated area of exogenous NMDA- and AMPA-induced currents. Moreover NO changed the distribution of miniature EPSC amplitude, but not frequency distribution in most neurons. N20 inhibits glutamatergic transmission in the superficial dorsal horn by modulating the NMDA- and AMPA-receptors. Our findings raise the possibility that the antinociceptive effect of N2O may be directly mediated at the level of the spinal cord. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.pain.2007.03.026

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Background: Although intrathecal administration of opioids produces antinociceptive effects in the spinal cord, it has not been established whether intrathecal opioid application more effectively terminates C fiber-mediated pain than A fiber-mediated pain. Here, the authors focus on the differences in opioid actions on A delta- and C-afferent responses.
Methods: Using the whole cell patch clamp technique, the authors investigated the presynaptic inhibitory actions of mu-, delta-, and K-opioid receptor agonists on primary afferent-evoked excitatory postsynaptic currents (EPSCs) in substantia gelatinosa neurons of adult rat spinal cord slices.
Results: The mu agonist DAMGO (0.1, 1 mu m) reduced the amplitude of glutamatergic monosynaptic A delta- or C fiber-evoked EPSCs. C fiber-evoked EPSCs were inhibited to a greater extent than AS fiber-evoked EPSCs. The 5 agonist DPDPE (1, 10 mu m) produced modest inhibition of A delta- or C fiber-evoked EPSCs. In contrast, the K agonist U69593 (1 mu m) did not affect the amplitude of either A delta or C fiber-evoked EPSCs.
Conclusions: These results indicate that opioids suppress excitatory synaptic transmission mainly through activation of mu receptors on primary afferent C fibers. Given that the substantia gelatinosa is the main termination of A delta and C fibers transmitting nociceptive information, the current findings may partially explain the different potency of opioid agonists.

DOI： 10.1097/01.anes.0000286985.80301.5e

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Language：Japanese   Publisher：新潟大学  

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Other Link： http://search.jamas.or.jp/link/ui/2008085860

Authorship：Corresponding author   Language：English   Publisher：Niigata University  

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