Central antinociceptive effects of mitragynine in mice: Contribution of descending noradrenergic and serotonergic systems

Mitragynine is a major alkaloidal constituent of young leaves of Mitragyna speciosa Korth, that is known to exhibit narcotic-like activity. In this study, we investigated the roles of central monoaminergic systems in the antinociceptive action of mitragynine by means of the tail-pinch and hot-plate tests in mice. Mitragynine (1.0-10 mu g) injected i.c.v. exerted a dose-dependent antinociceptive activity in both tests. The activity of mitragynine (10 mu g, i.c.v.) in the tail-pinch test was antagonized by reserpine, 6-hydroxydopamine plus nomifensine, and p-chlorophenylalanine treatment, whereas the antinociceptive activity of morphine (3 mu g) given i.c.v. in this test was attenuated by 6-hydroxydopamine plus nomifensine but not by p-chlorophenylalanine treatment. Moreover, the activity of i.c.v. mitragynine was also antagonized by the alpha(2)-adrenoceptor antagonist, idazoxan (10 mu g), and cyproheptadine (1 mu g) administered intrathecally (i.t.). On the other hand, the antinociceptive action of i.c.v. mitragynine (10 mu g) in the hot-plate test was abolished by reserpine and 6-hydroxydopamine plus nomifensine, but not by p-chlorophenylalanine treatment. This action was also antagonized by i.t. injection of idazoxan (10 mu g) These results suggest that both descending noradrenergic and serotonergic systems are involved in the antinociceptive activity of supraspinally administered mitragynine on the mechanical noxious stimulation, while the descending noradrenergic system predominantly contributes to the effect of supraspinal mitragynine on the thermal noxious stimulation. The mechanisms underlying the suppressive action of mitragynine on the nociceptive response may differ from those of morphine in mice.