Activation of cannabinoid CB2 receptors reduces hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. (19th May 2015)

• Record Type: Journal Article
• Authors: Fu, Weisi; Taylor, Bradley K.
• Is Part Of: Neuroscience letters. Volume 595(2015)
• Page Start: 1
• Page End: 6
• Publication Date: 2015-05-19
• Subjects: Pain -- CB2 receptor -- JWH-133 -- AM-630 -- Multiple sclerosis; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2015.04.002
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: CB2 receptor activation with JWH-133 reduces central neuropathic pain in mice. The site of anti-hyperalgesic action of JWH-133 includes the spinal cord. JWH-133 reduces hypersensitivity at doses that do not produce ataxia. First pre-clinical studies to promote CB2 for treatment of multiple sclerosis pain. 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 (10–100 μg) 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 (1–3 μg). 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.