title: Activation of cannabinoid CB2 receptors reduces hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.
abstract: Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that, a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Four weeks after induction of experimental autoimmune encephalomyelitis, we found that intrathecal administration of JWH-133 (10-100μg) dose-dependently reduced both mechanical and cold hypersensitivity without producing signs of sedation or ataxia. The anti-hyperalgesic effects of JWH-133 could be dose-dependently prevented by intrathecal co-administration of the CB2 antagonist, AM-630 (1-3μg). Our results suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of the spinal cord, to suppress the hypersensitivity associated with experimental autoimmune encephalomyelitis. These are the first pre-clinical studies to directly promote CB2 as a promising target for the treatment of central pain in an animal model of multiple sclerosis.
authors: Department of Physiology, School of Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA.
authors: Weisi
authors: W
authors: Fu
authors: Department of Physiology, School of Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA. Electronic address: brad.taylor@uky.edu.
authors: Bradley K
authors: BK
authors: Taylor
mesh_terms: D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D007211:Indoles; D043885:Receptor, Cannabinoid, CB2; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC; C094023:iodopravadoline
keywords: AM-630; CB(2) receptor; JWH-133; Multiple sclerosis; Pain