Partial sciatic nerve transection as a model of neuropathic pain: a qualitative and quantitative neuropathological...

One of the most commonly used experimental animal models for neuropathic pain is the chronic constriction injury (CCI) where four loose ligatures are tied around the sciatic nerve. One disadvantage of this model is the introduction of foreign material into the wound, which causes a local inflammatory reaction. Thus the distinction between the neuropathic and the inflammatory component of pain is difficult in this model. In order to produce a pure nerve lesion, we performed a partial sciatic nerve transection (PST; a modification of the Seltzer model) in female Sprague-Dawley rats and compared behavior and nerve pathology. These rats developed thermal hyperalgesia and mechanical allodynia comparable to the CCI model. Recovery of these symptoms was found between days 40 and 60 after the nerve lesion. Some animals still showed symptoms on day 101, which was associated with a neuroma formation. The main pathological findings in the endoneurium in nerve segments distal to the lesion were edema, loss of myelinated fibers and increase in endoneurial cells, especially macrophages. In the epineurium the number of macrophages was strikingly increased after CCI compared with PST, indicating that the response of the immune system is different in a structural lesion with and without foreign material. In conclusion, PST is a pure nerve injury model without an epineurial inflammatory component due to foreign material and is therefore well suited for studying the role of local endoneurial processes in the development and maintenance of neuropathic pain. Also, the importance of regeneration in the termination of hyperalgesia can convincingly be shown in this model.