Easing the Pain

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Science  19 Sep 2003:
Vol. 301, Issue 5640, pp. 1633
DOI: 10.1126/science.301.5640.1633b

Drugs currently used to treat neuropathic pain caused by damage in the nervous system typically produce side effects such as drowsiness and dizziness. Drugs that are directed at targets outside the central nervous system (CNS) could avoid such problems. Ibrahim et al. suggest that activating the CB2 cannabinoid receptor with a selective agonist could be an alternative treament. The CB2 receptor is not found in the CNS but is expressed primarily on mast and immune cells. An aminoalkylindole called AM1241 was shown to be a selective CB2 agonist. Administration of the drug reversed sensory hypersensitivity observed in a rat model of neuropathic pain. In this rat model, spinal nerve ligation increases sensitivity to tactile and thermal stimuli, two characteristics of human neuropathic pain that can result from injury or disease of primary afferent neurons. In mice lacking the CB1 receptor, AM1241 was still able to block pain, indicating the specificity of the effect through CB2 receptors. AM1241 could have an antiinflammatory effect on mast and immune cells that would otherwise release mediators that sensitize primary afferent neurons. — LDC

Proc. Natl. Acad. Sci. U.S.A. 100, 10529 (2003).

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