4.6 Article

Mechanical hyperalgesia after an L5 spinal nerve lesion in the rat is not dependent on input from injured nerve fibers

期刊

PAIN
卷 85, 期 3, 页码 493-502

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/S0304-3959(00)00250-5

关键词

mechanical hyperalgesia; L5 ligation; dorsal rhizotomy; dermatome; neuropathic pain; wallerian degeneration

资金

  1. NICHD NIH HHS [HD33990] Funding Source: Medline
  2. NINDS NIH HHS [NS32386] Funding Source: Medline

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An injury to a peripheral nerve in animals often leads to signs of neuropathic pain including hyperalgesia to heat, cold and mechanical stimuli. The role of injured and intact nerve fibers in mechanical hyperalgesia was evaluated in rats subjected to an L5 spinal nerve ligation-and-cut ('modified SNL lesion'). To assess the contribution of injured afferents, an L5 dorsal rhizotomy was performed immediately before, or 7 days after the modified SNL lesion. To study the role of adjacent intact spinal nerves, an L4 dorsal rhizotomy was performed 7 days after the modified SNL lesion. The up-down method of Dixon (Dixon WJ, Annu Rev Pharmacol Toxicol 1980;20:441-462) was used to measure the paw withdrawal threshold to mechanical stimuli at three sites on the rat hindpaw corresponding to the L3, L4, and L5 dermatomes. We found that the modified SNL lesion produced a significant, lasting (>20 days) decrease of the mechanical withdrawal threshold. The severity and duration of mechanical hyperalgesia varied across testing sites. The L5 and JA dermatome test sites developed the most severe and lasting mechanical hyperalgesia. In contrast, the L3 testing site developed significantly less severe and shorter lasting mechanical hyperalgesia. L5 dorsal rhizotomy, by itself, produced a transient decrease in mechanical withdrawal thresholds. L5 dorsal rhizotomy performed before, or 7 days after, the modified SNL lesion did not prevent or resolve the observed decrease in mechanical withdrawal thresholds. L4 dorsal rhizotomy performed 7 days after the modified SNL lesion resulted in an immediate reversal of mechanical withdrawal thresholds back to baseline values. These results suggest that, after L5 spinal nerve ligation-and-cut, mechanical hyperalgesia develops and persists independent of input from injured afferents. We propose that the Wallerian degeneration that develops after a nerve injury leads to interactions between the degenerating fibers of the injured spinal nerve and the intact fibers of adjacent spinal nerves. This leads to changes in the intact fibers that play a critical role for both initiation and maintenance of mechanical hyperalgesia. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

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