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Neurosci Lett. 2015 May 19;595:1-6. doi: 10.1016/j.neulet.2015.04.002. Epub 2015 Apr 3.

Activation of cannabinoid CB2 receptors reduces hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

Author information

1
Department of Physiology, School of Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA.
2
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.

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.

KEYWORDS:

AM-630; CB(2) receptor; JWH-133; Multiple sclerosis; Pain

PMID:
25849525
PMCID:
PMC4464808
DOI:
10.1016/j.neulet.2015.04.002
[Indexed for MEDLINE]
Free PMC Article

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