Prostaglandin 15d-PGJ2 targets PPARγ and opioid receptors to prevent muscle hyperalgesia in rats.

Autor:	Santos DFS; Health, School of Applied Sciences, State University of Campinas-UNICAMP, Limeira, São Paulo, Brazil.; Department of Anesthesiology and Perioperative Medicine, Pittsburgh Center for Pain Research, Pittsburgh Project to end Opioid Misuse, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Melo-Aquino B; Health, School of Applied Sciences, State University of Campinas-UNICAMP, Limeira, São Paulo, Brazil., Jorge CO; Health, School of Applied Sciences, State University of Campinas-UNICAMP, Limeira, São Paulo, Brazil., Clemente-Napimoga JT; Laboratory of Neuroimmune Interface of Pain, Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo, Brazil., Taylor BK; Department of Anesthesiology and Perioperative Medicine, Pittsburgh Center for Pain Research, Pittsburgh Project to end Opioid Misuse, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Oliveira-Fusaro MCG; Health, School of Applied Sciences, State University of Campinas-UNICAMP, Limeira, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Neuroreport [Neuroreport] 2021 Feb 03; Vol. 32 (3), pp. 238-243.
DOI:	10.1097/WNR.0000000000001575
Abstrakt:	Pharmacological agents directed to either opioid receptors or peroxisome proliferator-activated receptor gamma (PPARγ) at peripheral tissues reduce behavioral signs of persistent pain. Both receptors are expressed in muscle tissue, but the contribution of PPARγ activation to muscle pain and its modulation by opioid receptors remains unknown. To address this question, we first tested whether the endogenous PPARγ 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-deoxyΔ-12,14-prostaglandin J2 (15d-PGJ2) was PPARγ- 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 PPARγ antagonist, 2-chloro-5-nitro-N-phenylbenzamide, or by the opioid receptor antagonist, naloxone. We conclude that 15d-PGJ2 targets PPARγ and opioid receptors to prevent muscle hyperalgesia. We suggest that local PPARγ receptors are important pharmacological targets for inflammatory muscle pain. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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