Antinociceptive and motor effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats

This study investigated antinociceptive effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats. Each animal received intrathecally, on 3 separate occasions (i) 2 μg morphine (M), (ii) a dose (D) of one of the non-opioid drugs, and (iii) a combination, 1 2(M + D), consisting of 1 μg morphine plus half the dose of the non-opioid drug. Antinociceptive effects were assessed by the hot-plate and tail-flick tests over the duration of drug action. All non-opioid drugs studied led to dose-related antinociceptive effects when given alone. Addition of morphine caused a left shift in the dose-response curves of all the non-opioid drugs, indicating at least some degree of additive effects. Effects were considered supra-additive when the effect of the combination, 1 2(M + D), was significantly greater than both the effect of 2 μg morphine and the dose of non-opioid. Evidence of supra-additive antinociceptive effects was obtained only with the clonidine-morphine combination.