Evidence for antinociceptive effects of combined administration of vitamin E and celecoxib in tail-flick and formalin test in male rats

Background: The aim of this study was to evaluate the effect of vitamin E co-administration with celecoxib in thermal and inflammatory pain in two model of pain assessment including thermal tail flick test of acute pain and formalin induced inflammatory model in adult male rats.

Methods: Seventy two male Wistar rats were divided into a vehicle received intraperitoneally olive oil, indomethacin (20 mg/kg), vitamin E (100, 200 and 400 mg/kg), celecoxib (3, 10, 30 and 60 mg/kg) groups, and combination groups received the combination of vitamin E (100 and 200 mg/kg) and celecoxib (3, 10 and 30 mg/kg). All drugs were dissolved in olive oil. Antinociceptive effect in tail-flick was measured using Area Under Curve (AUC) of responses and Maximum Possible Effect (%MPE) and pain score was used for antinociceptive response in formalin test.

Results: Vitamin E and celecoxib changed time course of pain scores in a dose related manner in formalin test but not in tail-flick test. Vitamin E (200 mg/kg) had no effect and merely 60 mg/kg of celecoxib increased %MPE and AUC in tail-flick. The combination of vitamin E (100 or 200 mg/kg) with celecoxib (3 or 10 mg/kg) decreased pain scores compared to vehicle in both phases of formalin test, while in chronic phase (II) the pain scores of combination groups were also decreased compared to vitamin E and celecoxib. However, in tail-flick test the combination of ineffective doses of vitamin E (200 mg/kg) and celecoxib (10 and 30 mg/kg) increased %MPE and AUC compared to vehicle but not compared to celecoxib or vitamin E.

Conclusions: Vitamin E and celecoxib showed a dose related antinociceptive effect in inflammatory but not in thermal model of acute pain. However the co-administration of vitamin E with celecoxib caused a significant increase in the antinociceptive effect which was similar to indomethacin, as a standard anti-inflammatory drug. So we suggest the concomitant use of vitamin E with celecoxib and other NSAIDs for potentiation of both anti- inflammatory and analgesic response, as well as the reduction of cardiovascular side effects of celecoxib.