Actions of midazolam on excitatory transmission in dorsal horn neurons of 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.
Kohno
Tatsuro
T
Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi, Niigata 951-8510, Japan. kohno-t@umin.ac.jp
Wakai
Ayako
A
Ataka
Toyofumi
T
Ikoma
Miho
M
Yamakura
Tomohiro
T
Baba
Hiroshi
H
D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008874:Midazolam / Q000494:pharmacology*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013126:Spinal Nerve Roots / Q000166:cytology / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000759:Adjuvants, Anesthesia; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D006993:Hypnotics and Sedatives; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008874:Midazolam; D001640:Bicuculline