Antinociceptive action of mitragynine in mice: Evidence for the involvement of supraspinal opioid receptors

Mitragynine is a major alkaloidal constituent extracted from the young leaves of Mitragyna speciosa Korth. (Rubiaceae). We investigated an antinociceptive activity of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection of this alkaloid by the tail-pinch and hot-plate tests in mice, and evaluated the mechanisms of the action using naloxone, an opioid receptor antagonist. Mitragynine (5.0-30 mg/kg, i.p. and 1.0-10 mu g/mouse, i.c.v.) exerted a dose-dependent antinociceptive activity which was maximal at 15-45 min after injection in the tail-pinch and hot-plate tests, but it did not induce a morphine-like behavioral change. The antinociceptive actions of i.p. mitragynine were completely abolished by both s.c. (2 mg/kg) and i.c.v (10 mg/mouse) naloxone. The action of i.c.v. mitragynine (10 mu g/mouse) was also antagonized by i.c.v. naloxone (10 mu g/mouse). These results indicate that mitragynine itself can induce antinociception by acting in the brain, and that the supraspinal opioid systems are at least partly involved in the antinociceptive action of mitragynine in mice.