Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices.
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.
Kohno
T
T
Department of Anesthesiology, Niigata University School of Medicine, Japan.
Kumamoto
E
E
Baba
H
H
Ataka
T
T
Okamoto
M
M
Shimoji
K
K
Yoshimura
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D005998:Glycine / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008874:Midazolam / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013376:Substantia Gelatinosa / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018757:GABA Modulators; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; D008874:Midazolam; D005998:Glycine