κ-Opioid receptor participates of NSAIDs peripheral antinociception

• Published in: Neuroscience letters 2016-05, Vol.622, p.6-9
• Main Authors: Silva, Lívia Caroline Resende, Castor, Marina Gomes Miranda e, Navarro, Larissa Caldeira, Romero, Thiago Roberto Lima, Duarte, Igor Dimitri Gama
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Anti-inflammatory drugs (NSAIDs); Diclofenac - pharmacology; Diclofenac - therapeutic use; Dinoprostone; Dipyrone - pharmacology; Dipyrone - therapeutic use; Hindlimb; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Hyperalgesia - physiopathology; Male; Naloxone - pharmacology; Opioid system; Peripheral antinociception; Rats, Wistar; Receptors, Opioid, delta - antagonists & inhibitors; Receptors, Opioid, kappa - antagonists & inhibitors; Receptors, Opioid, kappa - metabolism; Receptors, Opioid, mu - antagonists & inhibitors
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.04.029

•NSAIDs represent some of the most widely prescribed drugs.•The opioids participation in the peripheral antinociception by NSAIDs is unclear.•Opioid shared in the NSAIDs-induced antinociception by κ-opioid receptor activation. NSAIDs represent some of the most widely prescribed drugs for relief of short-term fever, pain and inflammation. The participation of the opioid system in the peripheral is poorly understood. The aim of this study was evaluate the role of opioid system in the peripheral antinociception by diclofenac and dipyrone. To test this hypothesis, opioid receptor antagonists were evaluated using the rat paw pressure test, in which pain sensitivity is increased by intraplantar injection of prostaglandin E2 (PGE2, 2μg). Diclofenac (20μg/paw) and Dipyrone (40μg/paw) administered locally into the right paw elicited an antinociceptive effect. It was used naloxone (50μg/paw), a non-selective opioid receptor antagonist, which antagonized peripheral antinociception induced by diclofenac and dipyrone. Selectively, it was evaluated the μ-, δ- and κ-opioid receptor antagonists, respectively, clocinnamox (40μg/paw), naltrindole (50μg/paw) and nor-binaltorphimine (20, 40 and 80μg/paw). Our data indicated that only the κ-opioid antagonist was capable to reverse the peripheral antinociception by NSAIDs. The present results provide evidence that the opioid system participated in the diclofenac and dipyrone-induced peripheral antinociception by indirect activation of κ-opioid receptor probable by release of endogenous opioids such as dynorphins.