title: Peripheral and spinal activation of cannabinoid receptors by joint mobilization alleviates postoperative pain in mice.
abstract: The present study was undertaken to investigate the relative contribution of cannabinoid receptors (CBRs) subtypes and to analyze cannabimimetic mechanisms involved in the inhibition of anandamide (AEA) and 2-arachidonoyl glycerol degradation on the antihyperalgesic effect of ankle joint mobilization (AJM). Mice (25-35g) were subjected to plantar incision (PI) and 24h after surgery animals received the following treatments, AJM for 9min, AEA (10mg/kg, intraperitoneal [i.p.]), WIN 55,212-2 (1.5mg/kg, i.p.), URB937 (0.01-1mg/kg, i.p.; a fatty acid amide hydrolase [FAAH] inhibitor) or JZL184 (0.016-16mg/kg, i.p.; a monoacylglycerol lipase [MAGL] inhibitor). Withdrawal frequency to mechanical stimuli was assessed 24h after PI and at different time intervals after treatments. Receptor specificity was investigated using selective CB1R (AM281) and CB2R (AM630) antagonists. In addition, the effect of the FAAH and MAGL inhibitors on the antihyperalgesic action of AJM was investigated. AJM, AEA, WIN 55,212-2, URB937 and JZL184 decreased mechanical hyperalgesia induced by PI. The antihyperalgesic effect of AJM was reversed by pretreatment with AM281 given by intraperitoneal and intrathecal routes, but not intraplantarly. Additionally, intraperitoneal and intraplantar, but not intrathecal administration of AM630 blocked AJM-induced antihyperalgesia. Interestingly, in mice pretreated with FAAH or the MAGL inhibitor the antihyperalgesic effect of AJM was significantly longer. This article presents data addressing the CBR mechanisms underlying the antihyperalgesic activity of joint mobilization as well as of the endocannabinoid catabolic enzyme inhibitors in the mouse postoperative pain model. Joint mobilization and these enzymes offer potential targets to treat postoperative pain.
authors.affiliation: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil; Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil; Curso de Fisioterapia, Universidade do Sul de Santa Catarina, Campus Grande Florianópolis, Palhoça, SC, Brazil. Electronic address: daniel.martins4@unisul.br.
authors.forename: D F
authors.initials: DF
authors.lastname: Martins
authors.forename: L
authors.initials: L
authors.lastname: Mazzardo-Martins
authors.forename: F J
authors.initials: FJ
authors.lastname: Cidral-Filho
authors.forename: V M
authors.initials: VM
authors.lastname: Gadotti
authors.forename: A R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000818:Animals; D000843:Ankle Joint; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009068:Movement; D010149:Postoperative Pain / Q000378:metabolism* / Q000534:rehabilitation*; D010525:Peripheral Nerves / Q000378:metabolism*; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D043882:Receptors, Cannabinoid
keywords: 2-AG; 2-arachidonoyl glycerol; AEA; AJM; ANOVA; AUC; CBRs; ECB; FAAH; JM; MAGL; PI; VFF; acute pain; analysis of variance; anandamide; ankle joint mobilization; area under the curve; cannabinoid receptors; endocannabinoid; fatty acid amide hydrolase; joint mobilization; mice; monoacylglycerol lipase; passive mobilization; plantar incision; rehabilitation; von Frey filament