Effects of spinal naloxone and naltrindole on the antinociceptive action of intrathecally administered dexmedetomidine.

Intrathecally administered alpha-2 adrenoceptor and opioid agonists are well known to exert antinociceptive effects in humans and various animals. To examine the interaction of these two groups of agents in the spinal cord, we tested the effect of the opioid antagonists naloxone or naltrindole on the antinociceptive action of an intrathecally administered alpha-2 agonist, dexmedetomidine, using a formalin test in rats. 19 groups of Sprague-Dawley rats (250-300 g) were prepared with chronic intrathecal catheters and examined for the effects of agents on the formalin test. Each group contained 6 animals. 50 μl of 5% formalin was injected subcutaneously in the plantar surface of one hind paw. For each animal, the number of spontaneous flinches, characterized by rapid and brief withdrawal of the injected paw, were counted separately at 1-2 min, 5-6 min (phase 1), and at 5-min intervals thereafter up to 60 min (phase 2). Intrathecal dexmedetomidine (1 μg) maximally depressed the behavioral changes in both phase 1 and phase 2 of the formalin test, which was antagonized by the alpha-2 adrenoceptor selective antagonist atipamezole (0.3 μg). Naloxone (0.1-10 μg) or naltrindole (1-10 μg), when coadministered with dexmedetomidine, showed a dose-dependent antagonism to the effect of dexmedetomidine, whereas naloxone, naltrindole, or atipamezole alone showed no effect on the nocieptive behavior due to formalin injection. These results indicate that the antinociceptive effect of intrathecally administered alpha-2 adrenoceptor agonists may involve opioid receptors in the spinal cord.