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 GABAA-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 GABAA 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 μM) 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 GABAA–benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.