title: The endocannabinoid system mediates aerobic exercise-induced antinociception in rats.
abstract: Exercise-induced antinociception is widely described in the literature, but the mechanisms involved in this phenomenon are poorly understood. Systemic (s.c.) and central (i.t., i.c.v.) pretreatment with CB₁ and CB₂ cannabinoid receptor antagonists (AM251 and AM630) blocked the antinociception induced by an aerobic exercise (AE) protocol in both mechanical and thermal nociceptive tests. Western blot analysis revealed an increase and activation of CB₁ receptors in the rat brain, and immunofluorescence analysis demonstrated an increase of activation and expression of CB₁ receptors in neurons of the periaqueductal gray matter (PAG) after exercise. Additionally, pretreatment (s.c., i.t. and i.c.v.) with endocannabinoid metabolizing enzyme inhibitors (MAFP and JZL184) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified this antinociceptive effect. These results indicate that exercise could activate the endocannabinoid system, producing antinociception. Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators (palmitoylethanolamide and oleoylethanolamide) were increased after AE. Therefore, these results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Ave. Antônio Carlos 6627, 31270-100 Belo Horizonte, Brazil. Electronic address: giovanegsouza@yahoo.com.br.
authors.forename: Giovane
authors.initials: G
authors.lastname: Galdino
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Ave. Antônio Carlos 6627, 31270-100 Belo Horizonte, Brazil.
authors.forename: Thiago R L
authors.initials: TR
authors.lastname: Romero
authors.affiliation: Department of Physiology, Institute of Biological Sciences, Federal University of Minas Gerais, Ave. Antônio Carlos 6627, 31270-100 Belo Horizonte, Brazil.
authors.forename: José Felipe P
authors.initials: JF
authors.lastname: Silva
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Ave. Antônio Carlos 6627, 31270-100 Belo Horizonte, Brazil.
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Aguiar
authors.affiliation: Biophotonics Lab, Department of Physics, Federal University of Minas Gerais, Ave. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: de Paula
authors.affiliation: Department of Biochemistry, Institute of Biological Sciences, Federal University of Minas Gerais, Ave. Antônio Carlos 6627, 31270-100 Belo Horizonte, Brazil.
authors.forename: Jader S
authors.initials: JS
authors.lastname: Cruz
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei 34, Compresorio Olivetti, 80078 Pozzuoli, Napoli, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Parrella
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei 34, Compresorio Olivetti, 80078 Pozzuoli, Napoli, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Ave. Antônio Carlos 6627, 31270-100 Belo Horizonte, Brazil.
authors.forename: Igor D
authors.initials: ID
authors.lastname: Duarte
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei 34, Compresorio Olivetti, 80078 Pozzuoli, Napoli, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Ave. Antônio Carlos 6627, 31270-100 Belo Horizonte, Brazil.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Perez
mesh_terms: D000698:Analgesia; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D063388:Endocannabinoids / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology; D010147:Pain Measurement; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D052117:Benzodioxoles; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D007211:Indoles; C534333:JZL 184; C462953:N-(2-methyl-3-hydroxyphenyl)-5,8,11,14-eicosatetraenamide; D063065:Organophosphonates; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C104810:methyl arachidonylfluorophosphonate; C103505:AM 251; C094023:iodopravadoline
keywords: Aerobic exercise; Antinociception; Cannabinoid receptors; Endocannabinoids; Pain