Interaction of midazolam and morphine in the spinal cord of the rat

The antinociceptive properties, as measured by the tail-flick and hot-plate tests, and the motor effects of an intrathecally-administered benzodiazepine agonist midazolam, alone, and in combination with morphine, was examined in rats. Midazolam alone produced a weak but dose-dependent (20-60 μg) antinociceptive effect in addition to a clear motor dysfunction at larger doses (60-100 μg). An inactive dose of intrathecally-administered midazolam (20 μg) produced a leftward shift in the dose-response curve for intrathecally administered morphine, in the thermal antinociceptive tests. This supra-additive effect was antagonized by naloxone (1 mg/kg). The data suggest a synergistic interaction between μ- and GABA_A-receptors in the spinal processing of thermally-evoked pain.