Endogenous opioids mediate the hypoalgesia induced by selective inhibitors of cyclo-oxygenase 2 in rat paws treated with carrageenan

• Published in: Neuropharmacology 2006-07, Vol.51 (1), p.37-43
• Main Authors: França, Dorothéa S., Ferreira-Alves, Dalton L., Duarte, Igor D.G., Ribeiro, Michel Campos, Rezende, Rafael Machado, Bakhle, Y.S., Francischi, Janetti N.
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics, Opioid - pharmacology; Animals; Carrageenan; Cyclooxygenase 1 - physiology; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase-2; Dinoprostone - administration & dosage; Dinoprostone - pharmacology; Drug Tolerance; Edema - chemically induced; Edema - complications; Endorphins - physiology; Foot; Hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - psychology; Indomethacin - pharmacology; Injections; Injections, Subcutaneous; Male; Morphine - pharmacology; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Opioids; Pain - drug therapy; Pain - etiology; Pain - physiopathology; Pain Measurement - drug effects; Prostaglandins; Pyrazoles - pharmacology; Rats; Rats, Sprague-Dawley; Rats, Wistar; Selective COX-2 inhibitors; Signal Transduction - drug effects; Species Specificity
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2006.02.012

Mechanical hyperalgesia induced in rat paws by carrageenan (250 μg) 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; 1–10 mg kg −1) decreased hyperalgesia but did not induce hypoalgesia. Pre-treatment with naltrexone (3 mg 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.