κ-Opioid receptor participates of NSAIDs peripheral antinociception.
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.
Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100, Belo Horizonte, MG, Brazil. Electronic address: liviaresendes@gmail.com.
Lívia Caroline Resende
LC
Silva
Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100, Belo Horizonte, MG, Brazil. Electronic address: marinacastor@gmail.com.
Marina Gomes Miranda E
MG
Castor
Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100, Belo Horizonte, MG, Brazil. Electronic address: laricnavarro@gmail.com.
Larissa Caldeira
LC
Navarro
Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100, Belo Horizonte, MG, Brazil. Electronic address: thiromero@ufmg.br.
Thiago Roberto Lima
TR
Romero
Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627, Pampulha, CEP 31.270-100, Belo Horizonte, MG, Brazil. Electronic address: dimitri@icb.ufmg.br.
Igor Dimitri Gama
ID
Duarte
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D004008:Diclofenac / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone; D004177:Dipyrone / Q000494:pharmacology* / Q000627:therapeutic use; D006614:Hindlimb; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004008:Diclofenac; D009270:Naloxone; D004177:Dipyrone; D015232:Dinoprostone
Anti-inflammatory drugs (NSAIDs); Opioid system; Peripheral antinociception