• Oliveira Cristina da Costa CDC Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Braz, Marina Gomes Miranda E Castor, Camila Gomes Miranda E Castor, Ághata de França Costa, Ferreira Renata Cristina Mendes RCM Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais,, Silva Josiane Fernandes da JFD Department of Physiology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil., Juliana Maria Navia Pelaez, Luciano Dos Santos Aggum Capettini, Virginia Soares Lemos, Duarte Igor Dimitri Gama IDG Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil, Perez Andrea de Castro AC Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Santos Sérgio Henrique Sousa SHS Department of Physiology, Institute of Biological Sciences, UFMG, Belo Horizonte, Minas Gerais, Brazil., and Romero Thiago Roberto Lima TRL Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Braz.
• Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
• Toxicol. Appl. Pharmacol. 2019 Apr 15; 369: 30-38.

AbstractDespite all the development of modern medicine, around 100 compounds derived from natural products were undergoing clinical trials only at the end of 2013. Among these natural substances in clinical trials, we found the resveratrol (RES), a pharmacological multi-target drug. RES analgesic properties have been demonstrated, although the bases of these mechanisms have not been fully elucidated. The aim of this study was to evaluate the involvement of opioid and cannabinoid systems in RES-induced peripheral antinociception. Paw withdrawal method was used and hyperalgesia was induced by carrageenan (200 μg/paw). All drugs were given by intraplantar injection in male Swiss mice (n = 5). RES (100 μg/paw) administered in the right hind paw induced local antinociception that was antagonized by naloxone, non-selective opioid receptor antagonist, and clocinnamox, μOR selective antagonist. Naltrindole and nor-binaltorfimine, selective antagonists for δOR and kOR, respectively, did not reverse RES-induced peripheral antinociception. CB1R antagonist AM251, but not CB2R antagonist AM630, antagonized RES-induced peripheral antinociception. Peripheral antinociception of RES intermediate-dose (50 μg/paw) was increased by: (i) bestatin, inhibitor of endogenous opioid degradation involved-enzymes; (ii) MAFP, inhibitor of anandamide amidase; (iii) JZL184, inhibitor of 2-arachidonoylglycerol degradation involved-enzyme; (iv) VDM11, endocannabinoid reuptake inhibitor. Acute and peripheral administration of RES failed to affect the amount of μOR, CB1R and CB2R. Experimental data suggest that RES induces peripheral antinociception through μOR and CB1R activation by endogenous opioid and endocannabinoid releasing.Copyright © 2019 Elsevier Inc. All rights reserved.

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