Nerve Injury-related Autoimmunity Activation Leads to Chronic Inflammation and Chronic Neuropathic Pain

Abstract

Abstract Background: Peripheral nerve injuries that provoke neuropathic pain are associated with chronic inflammation and nervous lesions. The authors hypothesized that chronic neuropathic pain might be caused by chronic inflammation resulting from a nervous autoimmune reaction triggered by nerve injury. Methods: The authors observed chronic inflammation and neuropathic behaviors for up to 12 weeks after nerve injury in T lymphocyte-deficient nude mice and their heterozygous littermates. Lymphocyte proliferation and Schwann cell apoptosis were examined after coculture of each population with various neural tissues from normal rats and those with nerve injury. Result: Nude mice recovered faster and exhibited less thermal hyperalgesia after nerve injury compared to their heterozygous littermates. A large number of IL-17+ cells indicative of lymphocyte activation were found in the injured sciatic nerve and spinal cord (L4-6) of heterozygous littermates, but far fewer of these populations were found in nude mice. In vitro lymphocyte proliferation was enhanced after coculture with nerve tissues from normal rats compared to nerve tissue-free phosphate-buffered saline controls. In particular, coculture with sciatic nerve tissue enhanced proliferation by 80%, dorsal root ganglion by 46%, and spinal cord by 14%. Moreover, neural tissues from rats with nerve injury markedly increased the lymphocyte proliferation compared to coculture with tissues from corresponding normal rats. Schwann cell apoptosis was triggered in vitro when cocultured with lymphocytes from neuropathic rats. Conclusion: Our study suggests that chronic neuropathic pain might be caused by chronic inflammation resulting from a nervous autoimmune reaction triggered by nerve injury.