Actions of Midazolam on Excitatory Transmission in Dorsal Horn Neurons of Adult Rat Spinal Cord

2006 ◽  
Vol 104 (2) ◽  
pp. 338-343 ◽  
Author(s):  
Tatsuro Kohno ◽  
Ayako Wakai ◽  
Toyofumi Ataka ◽  
Miho Ikoma ◽  
Tomohiro Yamakura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Benzodiazepine Receptor ◽  
Gamma Aminobutyric Acid ◽  
Excitatory Postsynaptic Currents ◽  
Adult Rat ◽  
Dorsal Horn Neurons ◽  
Postsynaptic Currents ◽  
Excitatory Transmission ◽  
Adult Rat Spinal Cord

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 II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. Results Bath-applied midazolam (1 microm) diminished Adelta- and C-fiber evoked polysynaptic excitatory postsynaptic currents in both amplitude and integrated area. However, it affected neither Adelta- 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 microm), midazolam (1 microm) did not diminish Adelta-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.

Action of Isoflurane on the Substantia Gelatinosa Neurons of the Adult Rat Spinal Cord

2005 ◽  
Vol 102 (2) ◽  
pp. 379-386 ◽  
Author(s):  
Ayako Wakai ◽  
Tatsuro Kohno ◽  
Tomohiro Yamakura ◽  
Manabu Okamoto ◽  
Toyofumi Ataka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Rat Spinal Cord ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Transmission ◽  
Adult Rat ◽  
Postsynaptic Currents ◽  
Acid Type ◽  
Adult Rat Spinal Cord

Background Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immobility 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.

Enflurane Directly Depresses Glutamate AMPA and NMDA Currents in Mouse Spinal Cord Motor Neurons Independent of Actions on GABAAor Glycine Receptors

2000 ◽  
Vol 93 (4) ◽  
pp. 1075-1084 ◽  
Author(s):  
Gong Cheng ◽  
Joan J. Kendig
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Glutamate Receptors ◽  
Dorsal Horn ◽  
Motor Neurons ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Anesthetic Concentration

Background The spinal cord is an important anatomic site at which volatile agents act to prevent movement in response to a noxious stimulus. This study was designed to test the hypothesis that enflurane acts directly on motor neurons to inhibit excitatory synaptic transmission at glutamate receptors. Methods Whole-cell recordings were made in visually identified motor neurons in spinal cord slices from 1- to 4-day-old mice. Excitatory postsynaptic currents (EPSCs) or potentials (EPSPs) were evoked by electrical stimulation of the dorsal root entry area or dorsal horn. The EPSCs were isolated pharmacologically into glutamate N-methyl-d-aspartate (NMDA) receptor- and non-NMDA receptor-mediated components by using selective antagonists. Currents also were evoked by brief pulse pressure ejection of glutamate under various conditions of pharmacologic blockade. Enflurane was made up as a saturated stock solution and diluted in the superfusate; concentrations were measured using gas chromatography. Results Excitatory postsynaptic currents and EPSPs recorded from motor neurons by stimulation in the dorsal horn were mediated by glutamate receptors of both non-NMDA and NMDA subtypes. Enflurane at a general anesthetic concentration (one minimum alveolar anesthetic concentration) reversibly depressed EPSCs and EPSPs. Enflurane also depressed glutamate-evoked currents in the presence of tetrodotoxin (300 nm), showing that its actions are postsynaptic. Block of inhibitory gamma-aminobutyric acid A and glycine receptors by bicuculline (20 micrometer) or strychnine (2 micrometer) or both did not significantly reduce the effects of enflurane on glutamate-evoked currents. Enflurane also depressed glutamate-evoked currents if the inhibitory receptors were blocked and if either D,L-2-amino-5-phosphonopentanoic acid (50 micrometer) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (10 micrometer) was applied to block NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-kainate receptors respectively. Conclusions Enflurane exerts direct depressant effects on both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and NMDA glutamate currents in motor neurons. Enhancement of gamma-aminobutyric acid A and glycine inhibition is not needed for this effect. Direct depression of glutamatergic excitatory transmission by a postsynaptic action on motor neurons thus may contribute to general anesthesia as defined by immobility in response to a noxious stimulus.

Primary afferent-evoked slow EPSPs and responses to substance P of dorsal horn neurons in the adult rat spinal cord slices

1993 ◽  
Vol 46 (1-2) ◽  
pp. 407-409 ◽  
Author(s):  
Megumu Yoshimura ◽  
Toko Shimizu ◽  
Yohichi Yajiri ◽  
Hiroe Inokuchi ◽  
Syogoro Nishi
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Dorsal Horn ◽  
Rat Spinal Cord ◽  
Primary Afferent ◽  
Adult Rat ◽  
Dorsal Horn Neurons ◽  
Adult Rat Spinal Cord

Actions of Midazolam on GABAergic Transmission in Substantia Gelatinosa Neurons of Adult Rat Spinal Cord Slices

2000 ◽  
Vol 92 (2) ◽  
pp. 507-507 ◽  
Author(s):  
Tatsuro Kohno ◽  
Eiichi Kumamoto ◽  
Hiroshi Baba ◽  
Toyofumi Ataka ◽  
Manabu Okamoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Benzodiazepine Receptor ◽  
Substantia Gelatinosa ◽  
Rat Spinal Cord ◽  
Gabaergic Transmission ◽  
Gaba A ◽  
Inhibitory Postsynaptic Currents ◽  
Adult Rat ◽  
Postsynaptic Currents ◽  
Adult Rat Spinal Cord

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 microM) 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 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); 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.

A-fiber sensory input induces neuronal cell death in the dorsal horn of the adult rat spinal cord

2001 ◽  
Vol 435 (3) ◽  
pp. 276-282 ◽  
Author(s):  
Richard E. Coggeshall ◽  
Helena A. Lekan ◽  
Fletcher A. White ◽  
Clifford J. Woolf
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Dorsal Horn ◽  
Sensory Input ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rat Spinal Cord ◽  
Adult Rat ◽  
Adult Rat Spinal Cord
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