Peripheral and spinal activation of cannabinoid receptors by joint mobilization alleviates postoperative pain in mice

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• 作者：D.F. Martins ; L. Mazzardo-Martins ; F.J. Cidral-Filho ; V.M. Gadotti ; A.R.S. Santos
• 关键词：2-AG ; 2-arachidonoyl glycerol ; AEA ; anandamide ; ANOVA ; analysis of variance ; AJM ; ankle joint mobilization ; AUC ; area under the curve ; CBRs ; cannabinoid receptors ; ECB ; endocannabinoid ; FAAH ; fatty acid amide hydrolase ; JM ; joint mobilization ; MAGL ; monoacylglycerol lipase ; PI ; plantar incision ; VFF ; von Frey filament
• 刊名：Neuroscience
• 出版年：26 December, 2013
• 年：2013
• 卷：255
• 期：Complete
• 页码：110-121
• 全文大小：1541 K

文摘

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 (25-35 g) were subjected to plantar incision (PI) and 24 h after surgery animals received the following treatments, AJM for 9 min, AEA (10 mg/kg, intraperitoneal [i.p.]), WIN 55,212-2 (1.5 mg/kg, i.p.), URB937 (0.01-1 mg/kg, i.p.; a fatty acid amide hydrolase [FAAH] inhibitor) or JZL184 (0.016-16 mg/kg, i.p.; a monoacylglycerol lipase [MAGL] inhibitor). Withdrawal frequency to mechanical stimuli was assessed 24 h 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.