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

Weisi Fu, Bradley K. Taylor

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalNeuroscience Letters
Volume595
DOIs
StatePublished - May 9 2015

Bibliographical note

Funding Information:
There are no financial or other relationships that might lead to a conflict of interest. Supported by NIHR01NS62306 and NIHK02DA19656, and University of Kentucky Start Up funds . We thank Mark Ingram with the University of Kentucky medical library for exhaustive literature searches. All authors have approved the final article. WF contributed in concept and study design, data acquisition and analysis, drafting and revising the manuscript. BKT contributed in obtaining funding for the project, concept and study design, data analysis, drafting and revising the manuscript.

Publisher Copyright:
© 2015 Elsevier Ireland Ltd.

Keywords

  • AM-630
  • CB receptor
  • JWH-133
  • Multiple sclerosis
  • Pain

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