Updated on 2024/04/16

写真a

 
OHASHI Nobuko
 
Organization
University Medical and Dental Hospital Anesthesiology Assistant Professor
Title
Assistant Professor
External link

Degree

  • 博士(医学) ( 2016.3   新潟大学 )

Research Areas

  • Life Science / Anesthesiology

Research History

  • Niigata University   University Medical and Dental Hospital Anesthesiology   Assistant Professor

    2016.4

Professional Memberships

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Papers

  • Omega-conotoxin MVIIA reduces neuropathic pain after spinal cord injury by inhibiting N-type voltage-dependent calcium channels on spinal dorsal horn

    Nobuko Ohashi, Daisuke Uta, Masayuki Ohashi, Rintaro Hoshino, Hiroshi Baba

    Frontiers in Neuroscience   18   2024.2

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    Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    Spinal cord injury (SCI) leads to the development of neuropathic pain. Although a multitude of pathological processes contribute to SCI-induced pain, excessive intracellular calcium accumulation and voltage-gated calcium-channel upregulation play critical roles in SCI-induced pain. However, the role of calcium-channel blockers in SCI-induced pain is unknown. Omega-conotoxin MVIIA (MVIIA) is a calcium-channel blocker that selectively inhibits N-type voltage-dependent calcium channels and demonstrates neuroprotective effects. Therefore, we investigated spinal analgesic actions and cellular mechanisms underlying the analgesic effects of MVIIA in SCI. We used SCI-induced pain model rats and conducted behavioral tests, immunohistochemical analyses, and electrophysiological experiments (in vitro whole-cell patch-clamp recording and in vivo extracellular recording). A behavior study suggested intrathecal MVIIA administration in the acute phase after SCI induced analgesia for mechanical allodynia. Immunohistochemical experiments and in vivo extracellular recordings suggested that MVIIA induces analgesia in SCI-induced pain by directly inhibiting neuronal activity in the superficial spinal dorsal horn. In vitro whole-cell patch-clamp recording showed that MVIIA inhibits presynaptic N-type voltage-dependent calcium channels expressed on primary afferent Aδ-and C-fiber terminals and suppresses the presynaptic glutamate release from substantia gelatinosa in the spinal dorsal horn. In conclusion, MVIIA administration in the acute phase after SCI may induce analgesia in SCI-induced pain by inhibiting N-type voltage-dependent calcium channels on Aδ-and C-fiber terminals in the spinal dorsal horn, resulting in decreased neuronal excitability enhanced by SCI-induced pain.

    DOI: 10.3389/fnins.2024.1366829

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  • Analgesic effect of ivabradine against inflammatory pain mediated by hyperpolarization-activated cyclic nucleotide–gated cation channels expressed on primary afferent terminals in the spinal dorsal horn

    Nobuko Ohashi, Daisuke Uta, Masayuki Ohashi, Hiroshi Baba

    Pain   163 ( 7 )   1356 - 1369   2022.7

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    Publishing type:Research paper (scientific journal)   Publisher:Ovid Technologies (Wolters Kluwer Health)  

    DOI: 10.1097/j.pain.0000000000002523

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  • Norepinephrine restores inhibitory tone of spinal lamina X circuitry, thus contributing to analgesia against inflammatory pain

    Nobuko Ohashi, Daisuke Uta, Masayuki Ohashi, Hiroshi Baba

    Neuroscience   2022.3

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

    DOI: 10.1016/j.neuroscience.2022.03.023

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  • Analgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action. Reviewed

    Front Pharmacol   11 ( 580289 )   2020.11

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  • Optimal Position of Inferior Vena Cava Cannula in Pediatric Cardiac Surgery: A Prospective, Randomized, Controlled, Double-Blind Study Reviewed International journal

    Yutaka Seino, Nobuko Ohashi, Hidekazu Imai, Hiroshi Baba

    Journal of Cardiothoracic and Vascular Anesthesia   33 ( 5 )   1253 - 1259   2019.5

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

    OBJECTIVE: To examine the authors' hypothesis that during the cardiopulmonary bypass (CPB) in children, the inferior vena cava cannula tip placed proximal to the right hepatic vein orifice would produce a higher venous drainage compared with that placed distally. DESIGN: A prospective, randomized, controlled, double-blind study. SETTING: Single university hospital. PARTICIPANTS: Thirty-two patients aged <6years, scheduled for elective cardiac surgery using CPB for congenital heart disease. INTERVENTIONS: Participants were randomized to 2 groups: the proximal group with the cannula tip placed proximally within 1cm of the right hepatic vein orifice and the distal group with the cannula placed distally within 1cm of the right hepatic vein orifice. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study was the perfusion flow rate at the time of establishment of total CPB with cardioplegia. The authors initially planned to enroll 60 patients, but before reaching the target sample size, the authors terminated this study owing to patient safety, and 18 patients in the proximal group and 14 patients in the distal group finally were analyzed. No significant differences in patient characteristics were observed between the 2 groups. The mean perfusion flow rate in the proximal group was significantly greater (2.55 ± 0.27 L/min/m2) than that in the distal group (2.37 ± 0.20 L/min/m2, p = 0.04). CONCLUSION: The inferior vena cava cannula tip placed in the proximal position was clinically superior, compared with a distal placement, in producing higher perfusion flow in children.

    DOI: 10.1053/j.jvca.2018.10.023

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  • Action of norepinephrine on lamina X of the spinal cord. Reviewed

    Neuroscience   1 ( 408 )   214 - 225   2019

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  • Pediatric Patients with High Pulmonary Arterial Pressure in Congenital Heart Disease Have Increased Tracheal Diameters Measured by Computed Tomography. International journal

    Nobuko Ohashi, Hidekazu Imai, Yutaka Seino, Hiroshi Baba

    Journal of cardiothoracic and vascular anesthesia   32 ( 4 )   1676 - 1681   2018.8

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

    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.

    DOI: 10.1053/j.jvca.2017.12.004

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  • The endogenous agonist, β-alanine, activates glycine receptors in rat spinal dorsal neurons. International journal

    Yutaka Seino, Nobuko Ohashi, Tatsuro Kohno

    Biochemical and biophysical research communications   500 ( 4 )   897 - 901   2018.6

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

    β-alanine is a structural analog of glycine and γ-aminobutyric acid (GABA) and is thought to be involved in the modulation of nociceptive information at the spinal cord. However, it is not known whether β-alanine exerts its effect in substantia gelatinosa (SG) neurons of the spinal dorsal horn, where glycine and GABA play an important role in regulating nociceptive transmission from the periphery. Here, we investigated the effects of β-alanine on inhibitory synaptic transmission in adult rat SG neurons using whole-cell patch-clamp. β-alanine dose-dependently induced outward currents in SG neurons. Current-voltage plots revealed a reversal potential at approximately -70 mV, which was close to the equilibrium potential of Cl-. Pharmacological analysis revealed that β-alanine activates glycine receptors, but not GABAA receptors. These results suggest that β-alanine hyperpolarizes the membrane potential of SG neurons by activating Cl- channels through glycine receptors. Our findings raise the possibility that β-alanine may modulate pain sensation through glycine receptors.

    DOI: 10.1016/j.bbrc.2018.04.183

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  • Intraoperative Detection of Persistent Endoleak by Detecting Residual Spontaneous Echocardiographic Contrast in the Aneurysmal Sac During Thoracic Endovascular Aortic Repair. International journal

    Hidekazu Imai, Nobuko Ohashi, Takayuki Yoshida, Takeshi Okamoto, Nobutaka Kitamura, Takahiro Tanaka, Hiroshi Baba

    Anesthesia and analgesia   125 ( 2 )   417 - 420   2017.8

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

    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 < .001) and at 6 months postoperatively (40.0% vs 2.5%, respectively; P < .001). Intraoperative confirmation of the absence of SEC may identify patients at low risk for persistent endoleaks after thoracic endovascular aortic repair.

    DOI: 10.1213/ANE.0000000000002207

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  • Acetaminophen Metabolite N-Acylphenolamine Induces Analgesia via Transient Receptor Potential Vanilloid 1 Receptors Expressed on the Primary Afferent Terminals of C-fibers in the Spinal Dorsal Horn. Reviewed International journal

    Nobuko Ohashi, Daisuke Uta, Mika Sasaki, Masayuki Ohashi, Yoshinori Kamiya, Tatsuro Kohno

    Anesthesiology   127 ( 2 )   355 - 371   2017

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: The widely used analgesic acetaminophen is metabolized to N-acylphenolamine, which induces analgesia by acting directly on transient receptor potential vanilloid 1 or cannabinoid 1 receptors in the brain. Although these receptors are also abundant in the spinal cord, no previous studies have reported analgesic effects of acetaminophen or N-acylphenolamine mediated by the spinal cord dorsal horn. We hypothesized that clinical doses of acetaminophen induce analgesia via these spinal mechanisms. METHODS: We assessed our hypothesis in a rat model using behavioral measures. We also used in vivo and in vitro whole cell patch-clamp recordings of dorsal horn neurons to assess excitatory synaptic transmission. RESULTS: Intravenous acetaminophen decreased peripheral pinch-induced excitatory responses in the dorsal horn (53.1 ± 20.7% of control; n = 10; P < 0.01), while direct application of acetaminophen to the dorsal horn did not reduce these responses. Direct application of N-acylphenolamine decreased the amplitudes of monosynaptic excitatory postsynaptic currents evoked by C-fiber stimulation (control, 462.5 ± 197.5 pA; N-acylphenolamine, 272.5 ± 134.5 pA; n = 10; P = 0.022) but not those evoked by stimulation of Aδ-fibers. These phenomena were mediated by transient receptor potential vanilloid 1 receptors, but not cannabinoid 1 receptors. The analgesic effects of acetaminophen and N-acylphenolamine were stronger in rats experiencing an inflammatory pain model compared to naïve rats. CONCLUSIONS: Our results suggest that the acetaminophen metabolite N-acylphenolamine induces analgesia directly via transient receptor potential vanilloid 1 receptors expressed on central terminals of C-fibers in the spinal dorsal horn and leads to conduction block, shunt currents, and desensitization of these fibers.

    DOI: 10.1097/ALN.0000000000001700

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  • Administration of tranexamic acid to patients undergoing surgery for adolescent idiopathic scoliosis evokes pain and increases the infusion rate of remifentanil during the surgery. International journal

    Nobuko Ohashi, Masayuki Ohashi, Naoto Endo, Tatsuro Kohno

    PloS one   12 ( 3 )   e0173622   2017

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

    BACKGROUND: We recently reported that tranexamic acid (TXA) evokes pain in rats by inhibiting γ-aminobutyric acid and glycine receptors on neurons in the spinal dorsal horn. Although TXA is commonly used to reduce perioperative blood loss during various surgeries, its potential to induce intraoperative nociception, thereby increasing the need for more analgesics during surgery, has not been investigated. Therefore, this study aimed to investigate whether TXA evokes pain and increases the need for a higher infusion rate of remifentanil in patients undergoing surgery for adolescent idiopathic scoliosis (AIS). METHODS: Data were collected from patients with AIS who underwent posterior spinal fusion surgery from January 2008 to December 2015. All surgical procedures were performed under total intravenous anesthesia with propofol and remifentanil, by the same team of orthopedic surgeons and anesthesiologists at a single institution. Patients in the TXA group were administered TXA (loading and maintenance doses, 1000 mg and 100 mg/h) whereas those in the control group were not. Our primary outcome was the infusion rate of the intraoperative opioid analgesic remifentanil. RESULTS: The final analysis was based on data collected from 33 and 30 patients in the control and TXA groups, respectively. No differences were observed in the demographic data or the hemodynamic parameters between the two groups of patients. In the TXA group, the durations of surgery and anesthesia were shorter, intravascular fluid volume and total blood loss were lower, and the doses of fentanyl and ketamine administered were higher than they were in the control group (P < 0.05 for all). The mean infusion rate of intraoperative remifentanil was significantly higher in the TXA group than in the control group (control group: 0.23 ± 0.04 μg/kg/min; TXA group: 0.28 ± 0.12 μg/kg/min; P = 0.014). CONCLUSIONS: Patients who received TXA during the AIS surgery required a higher infusion rate of remifentanil, indicating that TXA evoked pain during the surgery.

    DOI: 10.1371/journal.pone.0173622

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  • Ultrasound-guided ilioinguinal/iliohypogastric block did not reduce emergence delirium after ambulatory pediatric inguinal hernia repair: a prospective randomized double-blind study.

    Nobuko Ohashi, Sadahei Denda, Kenta Furutani, Takayuki Yoshida, Yoshinori Kamiya, Reiko Komura, Hironobu Nishimaki, Yasushi Iinuma, Yutaka Hirayama, Shinichi Naitou, Koju Nitta, Hiroshi Baba

    Surgery today   46 ( 8 )   963 - 9   2016.8

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    PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.01). CONCLUSIONS: 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.

    DOI: 10.1007/s00595-015-1280-6

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  • トラネキサム酸の脊髄後角を介する痛みの機序の解明 Reviewed

    大橋 宣子, 佐々木 美佳, 大橋 正幸, 紙谷 義孝, 馬場 洋, 河野 達郎

    PAIN RESEARCH   31 ( 1 )   9 - 20   2016.3

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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。

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J02781&link_issn=&doc_id=20160414560002&doc_link_id=%2Fci3painr%2F2016%2F003101%2F002%2F0009-0020%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fci3painr%2F2016%2F003101%2F002%2F0009-0020%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Tranexamic acid evokes pain by modulating neuronal excitability in the spinal dorsal horn. Reviewed International journal

    Nobuko Ohashi, Mika Sasaki, Masayuki Ohashi, Yoshinori Kamiya, Hiroshi Baba, Tatsuro Kohno

    scientific reports   5 ( 13458 )   13458 - 13458   2015

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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 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 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 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 in the spinal dorsal horn.

    DOI: 10.1038/srep13458

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  • Anesthetic management in a patient with giant growing teratoma syndrome: A case report Reviewed

    Nobuko Ohashi, Hidekazu Imai, Toshiyuki Tobita, Hideaki Ishii, Hiroshi Baba

    Journal of Medical Case Reports   8 ( 1 )   2014.1

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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.

    DOI: 10.1186/1752-1947-8-32

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  • 神経障害性疼痛患者に対するプレガバリン用量別の鎮痛効果と副作用 Reviewed

    大橋宣子, 清水大喜, 生駒美穂, 岡本 学, 河野達郎, 馬場 洋

    日本ペインクリニック学会誌   20 ( 4 )   500 - 502   2013.8

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

    DOI: 10.11321/jjspc.12-0045

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    Other Link: https://jlc.jst.go.jp/DN/JALC/10025432663?from=CiNii

  • Underlying mechanisms of pain evoked by tranexamic acid in the spinal dorsal horn neurons

    Ohashi Nobuko, Sasaki Mika, Ohashi Masayuki, Kamiya Yoshinori, Baba Hiroshi, Kohno Tatsuro

    PAIN RESEARCH   31 ( 1 )   9 - 20   2013

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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

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Books

  • トラネキサム酸による疼痛増強効果 -トラネキサム酸の脊髄後角を介する発痛作用の機序解明-

    Lisa: メディカル・サイエンス・インターナショナル  2018 

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  • 神経障害性痛の発生機序 脊髄での機序

    痛みのScience & Practice 8  2015 

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Awards

  • 有壬記念学術奨励賞

    2019  

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  • 日本麻酔科学会第65回学術集会 若手奨励賞 (基礎)

    2018   日本麻酔科学会  

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  • 新潟大学学長賞

    2018   新潟大学  

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Research Projects

  • イバブラジンの脊髄後角における作用機序解明と新規鎮痛薬としての有効性の検討

    Grant number:22K09041

    2022.4 - 2025.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    西塔 志乃, 大橋 宣子

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

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  • 脊髄損傷後疼痛における脊髄のシナプス可塑性変化の病態解明

    Grant number:22K09090

    2022.4 - 2025.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    大橋 宣子, 馬場 洋

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

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  • 脊髄損傷後疼痛におけるN型電位依存性Ca2+チャネルの役割と新規急性期治療の開発

    Grant number:21K09272

    2021.4 - 2024.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    大橋 正幸, 馬場 洋, 大橋 宣子

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    脊髄損傷は受傷時の脊髄への機械的損傷と、それに引き続く二次損傷により障害が重篤化することが知られている。二次障害においては細胞内Ca2+濃度上昇を伴う興奮毒性が関与しており、特にN型電位依存性Ca2+チャネルが重要な役割を担っている。そこで、ラット不全脊髄損傷モデルを用いて、脊髄損傷後急性期におけるN型電位依存性Ca2+チャネルの役割を運動および知覚機能の両面から解析した。脊髄損傷後4時間でN型電位依存性Ca2+チャネル阻害薬であるω-conotoxin MVIIAをくも膜下投与し、後肢運動機能 (Basso-Beattie-Bresnahan (BBB) score)と痛覚過敏 (von Frey test)を対照群と比較した。脊髄圧挫損傷を200kdyで加えた場合、後肢運動機能は損傷後3日の時点では投与群で有意にBBBスコアが高かったが、損傷後7日、14日では有意差を認めなかった。圧挫損傷100kdyでは、後肢運動機能は損傷後2日目を除いて損傷後1~7日まで投与群で有意にBBBスコアが高かったが、損傷後14日では有意差を認めなかった。また、von Frey testでは、損傷後14日の疼痛閾値は投与群で有意に高かった。以上から、脊髄損傷後急性期治療としてのN型電位依存性Ca2+チャネル阻害薬の有用性が、運動・知覚の両面から示唆された。一方で、運動機能に関しては損傷後1週間以降は投与群と対照群で有意差を認めなくなっており、次年度以降、複数回投与の効果についても検討予定である。また、本薬剤の効果について、電気生理学的実験、免疫組織学的実験、およびカルシウムイメージングにより多角的に検討を進める予定である。

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  • Norepinephrine restores inhibitory tone of spinal lamina X circuitry, thus contributing to analgesia against inflammatory pain

    Grant number:20K17777

    2020.4 - 2022.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

    Research category:Grant-in-Aid for Early-Career Scientists

    Awarding organization:Japan Society for the Promotion of Science

    Ohashi Nobuko

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    Noradrenaline (NA) is a neurotransmitter in descending pathways emanating from the brain stem and NA-containing fibers terminate in spinal lamina X, suggesting that NA may modulate nociceptive synaptic transmission in lamina X. We investigated this mechanism within inflammatory pain model rats.
    Using immunohistochemical staining and in vivo extracellular recording, the increased number of phosphorylated extracellular signal-regulated kinase profiles and increased frequency of spontaneous neuronal firing were significantly suppressed by the direct application of NA. Using in vitro patch-clamps recording, direct application of NA to spinal lamina X neurons facilitates frequency of miniature inhibitory postsynaptic current and induces an outward current, and these responses are inhibited by α1A- and α2-receptor antagonists. These mechanisms of NA on spinal lamina X might contribute to analgesia against inflammatory pain.

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  • Action of noradrenaline on lamina X of the spinal cord

    Grant number:19K24008

    2019.8 - 2021.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up

    Research category:Grant-in-Aid for Research Activity Start-up

    Awarding organization:Japan Society for the Promotion of Science

    Ohashi Nobuko

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    Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 )

    Lamina X is localized in the spinal cord within the region surrounding the central canal. Noradrenaline (NA) is a neurotransmitter in descending pathways emanating from the brain stem and NA-containing fibers terminate in lamina X, suggesting that NA may modulate nociceptive synaptic transmission in lamina X. Using spinal cord slices of inflammatory pain model rats and in vitro whole-cell patch-clamps, we found that NA acts 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. These mechanisms could be involved in the analgesia of NA on lamina X against inflammatory pain.

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  • Acetaminophen Metabolite N-Acylphenolamine Induces Analgesia via Transient Receptor Potential Vanilloid 1 Receptors Expressed on the Primary Afferent Terminals of C-fibers in the Spinal Dorsal Horn.

    Grant number:16K20081

    2016.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Research category:Grant-in-Aid for Young Scientists (B)

    Awarding organization:Japan Society for the Promotion of Science

    Ohashi Nobuko

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    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    Acetaminophen is metabolized to N-acylphenolamine (AM404), which induces analgesia in the brain, but no previous studies have reported analgesic effects of acetaminophen mediated by the spinal cord dorsal horn.
    First, we assessed in a rat using behavioral measures and revealed that systemic administration of acetaminophen and intrathecal injections of AM404 induces analgesia to thermal stimulation. Second, we used whole-cell patch-clamp recordings in the dorsal horn, and revealed that intravenous acetaminophen decreased peripheral pinch-induced excitatory responses, while direct application of acetaminophen did not reduce these responses. Direct application of AM404 decreased the amplitudes of monosynaptic EPSCs evoked by C-fibers stimulation. These phenomena were mediated by TRPV1, but not CB1, receptors.These results suggest that the acetaminophen metabolite AM404 induces analgesia directly via TRPV1 receptors expressed on central terminals of C-fibers in the spinal dorsal horn.

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