The role of focal nerve ischemia and Wallerian degeneration in peripheral nerve injury producing hyperesthesia.
BACKGROUND
A new model of pain associated with an experimental peripheral mononeuropathy has stimulated interest in mechanisms of pain and their structural correlates in peripheral nerve, the site of the experimental lesion.


METHODS
The pathology of the neuropathy was studied and the results correlated with alterations in nerve blood flow and with the behavioral response to heat applied to the foot. The focal neuropathy was created by loosely tying several ligatures around rat sciatic nerve, which produces hyperesthesia in the ligated limb in 3-5 days. The neuropathology was striking with epineurial and endoneurial vascular stasis, edema, and extensive nerve fiber injury in the ligated segment noted at 1 week after ligation.


RESULTS
Nerve blood flow was reduced significantly in the ligated segment during the development of the hyperesthesia response, suggesting that changes in nerve blood flow caused by the ligature compression of the epineurial vessels contributes to the nerve fiber injury and pathophysiology of the model. To further test this hypothesis, the epineurial vasculature was removed from 1-cm lengths of rat sciatic nerve, which reduces nerve blood flow by 58%, and by ligation of the ipsilateral femoral artery, which focally reduces nerve blood flow by 70%, and the behavioral response to heating of the paw was evaluated at 1 week. Crush injury was used as a positive control creating Wallerian degeneration without a substantial reduction in nerve blood flow.


CONCLUSIONS
The results suggest that ischemia is an important initial pathogenic mechanism in the hyperesthesia associated with the loose ligature pain model, in so far as it produces Wallerian degeneration and axonal injury. Modest degrees of ischemia producing only demyelination did not produce significant hyperesthesia.
Myers
R R
RR
Department of Anesthesiology, Veterans Administration Medical Center, San Diego 92161-9151.
Yamamoto
T
T
Yaksh
T L
TL
Powell
H C
HC
D000818:Animals; D005260:Female; D006941:Hyperesthesia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000098:blood supply*; D014855:Wallerian Degeneration / Q000502:physiology*