Multiple actions of systemic artemin for pain in experimental neuropathy.

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Abstract from Nat Med. 2003 Oct 5 [Epub ahead of print]. Epub 2003 Oct

05.

Multiple actions of systemic artemin in experimental neuropathy.

Gardell LR, Wang R, Ehrenfels C, Ossipov MH, Rossomando AJ, S,

Buckley C, Cai AK, Tse A, Foley SF, Gong B, Walus L, Carmillo P, Worley

D, Huang C, Engber T, Pepinsky

B, Cate RL, Vanderah TW, Lai J, Sah DW, Porreca F.

Department of Pharmacology, University of Arizona Health Sciences

Center, Tucson, Arizona 85724, USA.

The 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.