Effect of Celecoxib on the Peripheral NO Production

Abstract

Objective(s) Celecoxib acts through both COX-2-dependent and -independent pathways. According to the paradoxical effect of NO on the inflammatory and nociceptive signal processing, the present study designed to evaluate the probable contribution of NO in the analgesic and anti-inflammatory properties of celecoxib. Materials and Methods Different intensities of inflammatory pain were induced by acute and chronic sc administration of 1%, 2.5%, or 5% formalin and spectrophotometrical analysis of the serum nitrite was performed. Then, in the pretreatment process, the effect of celecoxib (10, 20, or 40 mg/kg/ip) was evaluated on the inflammatory pain induced-nitrite. Also, the effect of celecoxib alone (under non-inflammatory condition) was evaluated on the peripheral NO production and the results compared with that of the vehicle. Results Formalin-induced inflammatory pain led to an enhancement of the serum nitrite in intensity- and time- dependent manners. Celecoxib (40 mg/kg/ip), except its ineffectiveness on the nitrite level, induced 1.5 hr after 5% formalin, reduced production of formalin-induced nitrite in other cases. Meanwhile, under non‌inflammatory condition, 1.5 hr after the administration of celecoxib (40 mg/kg/ip), a considerable elevation of nitrite was observed. Celecoxib 10 or 20 mg/kg/ip did not show a significant effect on either inhibition or stimulation of the peripheral NO. Conclusion NO is involved both in the inflammatory and non-inflammatory conditions. It seems that celecoxib exerts a dual effect on the peripheral NO production; it prevents overproduction of NO due to the induction of inflammatory pain, while, it stimulates NO synthesis at the early stage of its action.