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Acute Resistance Exercise Induces Antinociception by Activation of the Endocannabinoid System in Rats

Galdino, Giovane PhD*; Romero, Thiago PhD*; Pinho da Silva, José Felippe PhD; Aguiar, Daniele PhD*; de Paula, Ana Maria PhD; Cruz, Jader PhD§; Parrella, Cosimo; Piscitelli, Fabiana PhD; Duarte, Igor PhD*; Di Marzo, Vincenzo PhD; Perez, Andrea PhD*

doi: 10.1213/ANE.0000000000000340
Pain and Analgesic Mechanisms: Research Report

BACKGROUND: Resistance exercise (RE) is also known as strength training, and it is performed to increase the strength and mass of muscles, bone strength, and metabolism. RE has been increasingly prescribed for pain relief. However, the endogenous mechanisms underlying this antinociceptive effect are still largely unexplored. Thus, we investigated the involvement of the endocannabinoid system in RE-induced antinociception.

METHODS: Male Wistar rats were submitted to acute RE in a weight-lifting model. The nociceptive threshold was measured by a mechanical nociceptive test (paw pressure) before and after exercise. To investigate the involvement of cannabinoid receptors and endocannabinoids in RE-induced antinociception, cannabinoid receptor inverse agonists, endocannabinoid metabolizing enzyme inhibitors, and an anandamide reuptake inhibitor were injected before RE. After RE, CB1 cannabinoid receptors were quantified in rat brain tissue by Western blot and immunofluorescence. In addition, endocannabinoid plasma levels were measured by isotope dilution-liquid chromatography mass spectrometry.

RESULTS: RE-induced antinociception was prevented by preinjection with CB1 and CB2 cannabinoid receptor inverse agonists. By contrast, preadministration of metabolizing enzyme inhibitors and the anandamide reuptake inhibitor prolonged and enhanced this effect. RE also produced an increase in the expression and activation of CB1 cannabinoid receptors in rat brain tissue and in the dorsolateral and ventrolateral periaqueductal regions and an increase in endocannabinoid plasma levels.

CONCLUSIONS: The present study suggests that a single session of RE activates the endocannabinoid system to induce antinociception.

Published ahead of print June 26, 2014.

From the *Department of Pharmacology, Department of Physiology, Institute of Biological Sciences, Department of Physics, and §Department of Biochemistry, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; and Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Pozzuoli, Napoli, Italy.

Published ahead of print June 26, 2014.

Accepted for publication April 17, 2014.

Funding: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de Minas Gerias (FAPEMIG), Brazil, and by the NIH, National Institute of Drug Abuse (DA-009789 to VD).

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Giovane Galdino, PhD, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos 6627, 31270-100 Belo Horizonte, Brazil. Address e-mail to

© 2014 International Anesthesia Research Society