ABSTRACT
AIMS: The endogenous opioids mediate the analgesic effects of celecoxib in a model of mechanical hyperalgesia in rats. As responses to thermal stimuli may differ from those to mechanical stimuli, we have here assessed celecoxib in a rat model of thermal hyperalgesia and the possible involvement of endogenous opioids and their corresponding receptors in these effects. MAIN METHODS: Injection of carrageenan (CG) into one hind paw induced a dose-related hyperalgesia (decreased time for paw withdrawal) to thermal stimuli (infra-red light beam), over 6h. KEY FINDINGS: Celecoxib (sc) 30 min before CG (250 microg per paw) induced a dose-dependent reversal of hyperalgesia, with withdrawal times well above basal levels, characterizing development of hypoalgesia. Indomethacin (sc) reversed CG-induced hyperalgesia only to basal levels (an anti-hyperalgesic effect). Naltrexone (sc) prevented hypoalgesia after celecoxib but did not change the response to indomethacin. Local (intraplantar) injection of either a selective antagonist of mu-(beta-funaltrexamine), kappa-(nor-binaltorphimine) or of delta-(naltrindole) opioid receptors also reversed the hypoalgesic effects of celecoxib, without modifying the hyperalgesia due to CG or affecting the nociceptive thresholds in the non-injected paw. SIGNIFICANCE: Our data show that celecoxib, unlike indomethacin, was hypoalgesic in this model of thermal hyperalgesia, and that this effect was mediated by peripheral mu-, kappa- and delta-opioid receptors.
