Peripheral mu-, kappa- and delta-opioid receptors mediate the hypoalgesic effect of celecoxib in a rat model of thermal hyperalgesia.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Correa
Jôice D
JD
Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Paiva-Lima
Patrícia
P
Rezende
Rafael M
RM
Dos Reis
Webster G P
WG
Ferreira-Alves
Dalton L
DL
Bakhle
Y S
YS
Francischi
Janetti N
JN
D000818:Animals; D002351:Carrageenan; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009292:Narcotic Antagonists; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use*; D013696:Temperature
D052246:Cyclooxygenase 2 Inhibitors; D009292:Narcotic Antagonists; D011720:Pyrazoles; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013449:Sulfonamides; D002351:Carrageenan; D000068579:Celecoxib