Dose Dependent effects of Celecoxib on CB-1 Agonist Induced Antinociception in mice

Objective: Endocannabinoid produces analgesia which is comparable to opioids. The antinociceptive effects of (Δ) - 9 tetrahydrocannabinol (THC) is suggested to be caused by cyclooxygenase (COX) pathway. In the present study, the effects of two extreme dose ranges of celecoxib (mg/kg and ng/kg), and 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 intrapritoneal(IP)). and ultra low dose (ULD) (25 and 50 ng/kg, IP) on the antinociceptive effect of intracerebroventricular (ICV) administration of ACPA (0.004, 0.0625 and 1 μg/mice) using formalin test in mice. Results: ICV 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 compared to the ultra-low dose of the drug.