Spared nerve injury: an animal model of persistent peripheral neuropathic pain

Peripheral neuropathic pain is produced by multiple etiological factors tha t initiate a number of diverse mechanisms operating at different sites and at different times and expressed both within, and across different disease states. Unraveling the mechanisms involved requires laboratory animal model s that replicate as far as possible, the different pathophysiological chang es present in patients. It is unlikely that a single animal model will incl ude the full range of neuropathic pain mechanisms. A feature of several ani mal models of peripheral neuropathic pain is partial denervation. In the mo st frequently used models a mixture of intact and injured fibers is created by loose ligation of either the whole (Bennett GJ, Xie YK. A peripheral mo noneuropathy in rat that produces disorders of pain sensation like those se en in man. Pain 1988;33:87-107) or a tight ligation of a part (Seltzer Z, D ubner R, Shir Y. A novel behavioral model of neuropathic pain disorders pro duced in rats by partial sciatic nerve injury. Pain 1990;43:205-218) of a l arge peripheral nerve, or a tight ligation of an entire spinal segmental ne rve (Kim SH, Chung JM. An experimental model for peripheral neuropathy prod uced by segmental spinal nerve ligation in the rat. Pain 1992;50.355-363). We have developed a variant of partial denervation, the spared nerve injury model. This involves a lesion of two of the three terminal branches of the sciatic nerve (tibial and common peroneal nerves) leaving the remaining su ral nerve intact. The spared nerve injury model differs from the Chung spin al segmental nerve, the Bennett chronic constriction injury and the Seltzer partial sciatic nerve injury models in that the co-mingling of distal inta ct axons with degenerating axons is restricted, and it permits behavioral t esting of the noninjured skin territories adjacent to the denervated areas. The spared nerve injury model results in early (<24 h), prolonged (>6 mont hs), robust tall animals are responders) behavioral modifications. The mech anical (von Frey and pinprick) sensitivity and thermal (hot and cold) respo nsiveness is increased in the ipsilateral sural and to a lesser extent saph enous territories, without any change in heat thermal thresholds. Crush inj ury of the tibial and common peroneal nerves produce similar early changes, which return, however to baseline at 7-9 weeks. The spared nerve injury mo del may provide, therefore, an additional resource for unraveling the mecha nisms responsible for the production of neuropathic pain. (C) 2000 Internat ional Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.