Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

Abstract

Objective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆) - 9 tetrahydrocannabinol (THC) is suggested to be through cyclooxygenase (COX) pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg), a cyclooxygenase-2 (COX-2) antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist) induced antinociception in mice was examined. Methods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.) and ultra low dose (ULD) (25 and 50 ng/kg, i.p.), on the antinociceptive effect of intracerebroventricular (i.c.v.) administration of ACPA (0.004, 0.0625 and 1 μg/mice), using formalin test in mice. Results: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg) and its ULD (ng/kg) attenuated and potentiated, ACPA antinociceptive effects, respectively. Conclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.