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Multiple actions of systemic artemin in experimental neuropathy

Abstract

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.

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Figure 1: Normalization of SNL-induced tactile and thermal hypersensitivity by systemic artemin, with administration beginning at the time of surgery.
Figure 2: Lack of tolerance to repeated artemin treatment in neuropathic pain.
Figure 3: Dose-related reversal of neuropathic pain by artemin.
Figure 4: Artemin normalizes SNL-induced neurochemical changes.
Figure 5: Systemic artemin normalized immunohistochemical markers in the ipsilateral L5 DRG, dorsal spinal cords and sciatic nerves of SNL rats.

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Acknowledgements

The authors thank S. Burgess, L. Majuta, K. Vault and C. Zhong for technical assistance; M. McAuliffe, B. Coleman and C. Tonkin for DNA sequencing; R. Boynton, A. Kaffashan, D. Mo, D. Wen and C. Young for protein sequencing and characterization; and the Biogen Media Preparation Group.

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Correspondence to Frank Porreca.

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These studies were supported by a grant from Biogen Inc.

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Gardell, L., Wang, R., Ehrenfels, C. et al. Multiple actions of systemic artemin in experimental neuropathy. Nat Med 9, 1383–1389 (2003). https://doi.org/10.1038/nm944

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