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 &mgr;m) diminished A&dgr;- and C-fiber evoked polysynaptic excitatory postsynaptic currents in both amplitude and integrated area. However, it affected neither A&dgr;- 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 &mgr;m), midazolam (1 &mgr;m) did not diminish A&dgr;-fiber evoked polysynaptic excitatory postsynaptic currents, suggesting that midazolam modulate the &ggr;-aminobutyric acid interneurons in the dorsal horn. Conclusions:Midazolam reduced excitatory synaptic transmission by acting on the &ggr;-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.