Faculty Profiles - BABA Hiroshsi

Papers - BABA Hiroshsi

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Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices

T Kohno, E Kumamoto, H Baba, T Ataka, M Okamoto, K Shimoji, M Yoshimura

ANESTHESIOLOGY 92 ( 2 ) 507 - 515 2000.2

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

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.

File： Midazolam(2000).pdf

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Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (Part 2) - Effects on somatodendritic sites of GABAergic neurons Reviewed

H Baba, PA Goldstein, M Okamoto, T Kohno, T Ataka, M Yoshimura, K Shimoji

ANESTHESIOLOGY 92 ( 2 ) 485 - 492 2000.2

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

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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Actions of midazolam on excitatory transmission in dorsal horn neurons of adult rat spinal cord Reviewed

Kohno T, Wakai A, Ataka T, Ikoma M, Yamakura T, Baba H

Anesthesiology 104 ( 2 ) 338 - 343 2000

Phosphorylation of ERK and CREB in nociceptive neurons after noxious stimulation Reviewed

RR Ji, GJ Brenner, R Schmoll, H Baba, CJ Woolf

PROCEEDINGS OF THE 9TH WORLD CONGRESS ON PAIN 16 191 - 198 2000

Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity Reviewed

Ru-Rong Ji, Hiroshi Baba, Gary J. Brenner, Clifford J. Woolf

Nature Neuroscience 2 ( 12 ) 1114 - 1119 1999.12

Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity Reviewed

RR Ji, H Baba, GJ Brenner, CJ Woolf

NATURE NEUROSCIENCE 2 ( 12 ) 1114 - 1119 1999.12

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 effectiveness of preemptive analgesia varies according to the type of surgery: A randomized, double-blind study Reviewed

S Aida, H Baba, T Yamakura, K Taga, S Fukuda, K Shimoji

ANESTHESIA AND ANALGESIA 89 ( 3 ) 711 - 716 1999.9

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

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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Peripheral inflammation facilitates A beta fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord Reviewed

H Baba, TP Doubell, CJ Woolf

JOURNAL OF NEUROSCIENCE 19 ( 2 ) 859 - 867 1999.1

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

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 < 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 < 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 < 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.

File： 859.full.pdf

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Muscarinic facilitation of GABA release in substantia gelatinosa of the rat spinal dorsal horn Reviewed

H Baba, T Kohno, M Okamoto, PA Goldstein, K Shimoji, M Yoshimura

JOURNAL OF PHYSIOLOGY-LONDON 508 ( 1 ) 83 - 93 1998.4

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

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.

File： Baba,Muscarinic(JP,1998).pdf

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Effects of fentanyl on spinal cord potentials and electromyogram evoked by transcranial magnetic stimulation in man Reviewed

T Tobita, S Denda, T Takada, H Endoh, H Baba, T Yamakura, S Fukuda, K Shimoji

RECENT ADVANCES IN HUMAN NEUROPHYSIOLOGY 1162 1034 - 1037 1998

Prior brain injury protects death from local anaesthetic-induced convulsion Reviewed

H Endoh, Y Kumagai, H Baba, T Yamakura, K Taga, K Sato, S Fukuda, K Shimoji

BRAIN RESEARCH 767 ( 1 ) 136 - 139 1997.8

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

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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Comparison of circulatory and respiratory responses between supplementary epidural buprenorphine and eptazocine administration during and immediately after total intravenous anesthesia Reviewed

S. Aida, H. Baba, K. Shimoji

Journal of Anesthesia 11 ( 2 ) 94 - 99 1997

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

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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Facilitation of GABA release by Carbachol and Neostigmine in Substantia Gelatinosa of Rat Spinal Cord Reviewed

Baba H, Kohno T, Okamoto M, Endoh H, Yamakura T, YoshimuraM, Shimoji K

Pain Research 12 ( 2 ) 65 - 72 1997

Somatosensory evoked potentials recorded from the posterior pharynx to stimulation of the median nerve and cauda equina Reviewed

T Takada, S Denda, H Baba, H Fujioka, T Yamakura, H Fujihara, K Taga, S Fukuda, K Shimoji

EVOKED POTENTIALS-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY 100 ( 6 ) 493 - 499 1996.11

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

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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Central nuclei and spinal pathways in feedback inhibitory spinal cord potentials in ketamine-anaesthetized rats Reviewed

S Denda, K Shimoji, M Tomita, H Baba, T Yamakura, H Masaki, H Endoh, S Fukuda

BRITISH JOURNAL OF ANAESTHESIA 76 ( 2 ) 258 - 265 1996.2

Language：English Publishing type：Research paper (scientific journal) Publisher：PROF SCI PUBL

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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Spinal tracts producing slow components of spinal cord potentials evoked by descending volleys in man Reviewed

M Tomita, K Shimoji, S Denda, T Tobita, S Uchiyama, H Baba

EVOKED POTENTIALS-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY 100 ( 1 ) 68 - 73 1996.1

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

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 < 0.05-P < 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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ROLE OF A-DELTA AFFERENT-FIBERS IN MODULATION OF PRIMARY AFFERENT INPUT TO THE ADULT-RAT SPINAL-CORD Reviewed

T SHIMIZU, M YOSHIMURA, H BABA, K SHIMOJI, H HIGASHI

BRAIN RESEARCH 691 ( 1-2 ) 92 - 98 1995.9

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

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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Patch Clamp Analysis of Serotonin Action on Substantia Gelatinosa Neurons in Adult Rat Spinal Cord

YOSHIMURA Megumu, MIZUKAMI Kiyoshi, OKAMOTO Manabu, BABA Hiroshi, HIGASHI Hideho

PAIN RESEARCH 10 ( 2 ) 51 - 60 1995.7

Noradrenaline alpha 1 receptors facilitate inhibitory transmitter release in substantia gelatinosa of the spinal cord Reviewed

H BABA, M OKAMOTO, M YOSHIMURA, K SHIMOJI

PROGRESS IN ANESTHETIC MECHANISM, VOL 3, SPECIAL ISSUE, 1995 314 - 317 1995

Management of a patient with severe kyphoscoliosis and postoperative respiratory failure Reviewed

Toshiyuki Tobita, Satoru Fukuda, Yuuichi Kumagai, Kiichiro Taga, Hiroshi Baba, Koki Shimoji

Journal of Anesthesia 8 ( 4 ) 490 - 492 1994.12

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Papers - BABA Hiroshsi