Editors' ChoicePharmacology

Easing the Pain

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Science's STKE  09 Sep 2003:
Vol. 2003, Issue 199, pp. tw342-TW342
DOI: 10.1126/stke.2003.199.tw342

Drugs currently used to treat neuropathic pain caused by damage in the nervous system typically cause side effects such as drowsiness and dizziness. Therefore, drugs 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 treatment. 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 specificity of the effect through CB2 receptors. The authors propose that AM1241 could have an anti-inflammatory effect on mast and immune cells that would normally release mediators that sensitize primary afferent neurons.

M. M. Ibrahim, H. Deng, A. Zvonok, D. A. Cockayne, J. Kwan, H. P. Mata, T. W. Vanderah, J. Laai, F. Porreca, A. Makriyannis, T. P. Malan Jr., Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: Pain inhibition by receptors not present in the CNS. Proc. Natl. Acad. Sci. U.S.A. 100, 10529-10533 (2003). [Abstract] [Full Text]

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