Nature Medicine
9, 1383 - 1389 (2003)
Published online: 5 October 2003; | doi:10.1038/nm944
Multiple actions of systemic artemin in experimental neuropathyLuis R Gardell1, Ruizhong Wang1, Chris Ehrenfels2, Michael H Ossipov1, Anthony J Rossomando2, Stephan Miller2, Carolyn Buckley2, Amber K Cai2, 3, Albert Tse2, Susan F Foley2, BangJian Gong2, Lee Walus2, Paul Carmillo2, Dane Worley2, Carol Huang2, 3, Thomas Engber2, Blake Pepinsky2, Richard L Cate2, Todd W Vanderah1, Josephine Lai1, Dinah W Y Sah2
& Frank Porreca11
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA. 2
Biogen Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA. 3
Present addresses: A.K.C. (11 Smith Hill Road, Lincoln, Massachusetts 01773, USA) and C.H. (874 Yorkchester Drive, Houston, Texas 77079, USA).
Correspondence should be addressed to Frank Porreca frankp@u.arizona.eduThe clinical management of neuropathic pain is particularly challenging. Current therapies for neuropathic pain modulate nerve impulse propagation or synaptic transmission; these therapies are of limited benefit and have undesirable side effects. Injuries to peripheral nerves result in a host of pathophysiological changes associated with the sustained expression of abnormal pain. Here we show that systemic, intermittent administration of artemin produces dose- and time-related reversal of nerve injury−induced pain behavior, together with partial to complete normalization of multiple morphological and neurochemical features of the injury state. These effects of artemin were sustained for at least 28 days. Higher doses of artemin than those completely reversing experimental neuropathic pain did not elicit sensory or motor abnormalities. Our results indicate that the behavioral symptoms of neuropathic pain states can be treated successfully, and that partial to complete reversal of associated morphological and neurochemical changes is achievable with artemin.
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