Agradecimentos: The authors thank Andrew H. Cooper and Tyler S. Nelson for proofreading this manuscript. This work was supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001, the Sao Paulo Research Foundation (FAPESP) (grant number 2011/11064-4) and National Institutes of Health R01NS62306, R01DA037621 and R01NS045954 to B.K.T. Ver menos

Abstract: Pharmacological agents directed to either opioid receptors or peroxisome proliferator-activated receptor gamma (PPAR?) at peripheral tissues reduce behavioral signs of persistent pain. Both receptors are expressed in muscle tissue, but the contribution of PPAR? activation to muscle pain and its modulation by opioid receptors remains unknown. To address this question, we first tested whether the endogenous PPAR? ligand 15d-PGJ2 would decrease mechanical hyperalgesia induced by carrageenan administration into the gastrocnemius muscle of rats. Next, we used receptor antagonists to determine whether the antihyperalgesic effect of 15-deoxy?-12,14-prostaglandin J2 (15d-PGJ2) was PPAR?- or opioid receptor-dependent. Three hours after carrageenan, muscle hyperalgesia was quantified with the Randall–Selitto test. 15d-PGJ2 prevented carrageenan-induced muscle hyperalgesia in a dose-dependent manner. The antihyperalgesic effect of 15d-PGJ2 was dose-dependently inhibited by either the PPAR? antagonist, 2-chloro-5-nitro-N-phenylbenzamide, or by the opioid receptor antagonist, naloxone. We conclude that 15d-PGJ2 targets PPAR? and opioid receptors to prevent muscle hyperalgesia. We suggest that local PPAR? receptors are important pharmacological targets for inflammatory muscle pain Ver menos