Endogenous opioids mediate the hypoalgesia induced by selective inhibitors of cyclo-oxygenase 2 in rat paws treated with carrageenan.
Mechanical hyperalgesia induced in rat paws by carrageenan (250microg) was modified by pre-treatment with three selective inhibitors of cyclo-oxygenase-2 (COX-2); celecoxib, rofecoxib and SC236. These inhibitors raised the nociceptive threshold above the normal, non-inflamed, level, inducing a state of hypoalgesia. Such hypoalgesia was observed in different strains of rat (Holtzman, Wistar and Sprague-Dawley) and after different modes of administration of the COX-2 inhibitor (locally, in the paw, or systemically). A selective inhibitor of COX-1 (SC 560; 1-10mg kg(-1)) decreased hyperalgesia but did not induce hypoalgesia. Pre-treatment with naltrexone (3mg kg(-1)), an opioid receptor antagonist, did not affect carrageenan-induced hyperalgesia but abolished the hypoalgesic effects of COX-2 inhibitors, without diminishing the anti-hyperalgesic effect of indomethacin. In rats made tolerant to the anti-nociceptive effects of morphine, all anti-nociceptive effects of SC236 were abolished but the anti-hyperalgesic effects of indomethacin or SC 560 were unaffected. We conclude that, in our model of inflammatory hyperalgesia, the anti-nociceptive effect of selective COX-2 inhibitors involved the participation of endogenous opioids.
França
Dorothéa S
DS
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Campus da Pampulha, 31270901 Belo Horizonte, Minas Gerais, Brazil.
Ferreira-Alves
Dalton L
DL
Duarte
Igor D G
ID
Ribeiro
Michel Campos
MC
Rezende
Rafael Machado
RM
Bakhle
Y S
YS
Francischi
Janetti N
JN
D000700:Analgesics; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan; D051545:Cyclooxygenase 1 / Q000502:physiology; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology; D004361:Drug Tolerance; D004487:Edema / Q000139:chemically induced / Q000150:complications; D004723:Endorphins / Q000502:physiology*; D005528:Foot; D006930:Hyperalgesia / Q000139:chemically induced / Q000523:psychology; D007213:Indomethacin / Q000494:pharmacology; D007267:Injections; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity
D000700:Analgesics; D000701:Analgesics, Opioid; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004723:Endorphins; D009292:Narcotic Antagonists; D011720:Pyrazoles; C115461:SC 560; D009271:Naltrexone; D009020:Morphine; D002351:Carrageenan; D051545:Cyclooxygenase 1; D015232:Dinoprostone; D007213:Indomethacin