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

Abstract

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 γ-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 μM) 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 μ♂) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 μM); 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.