Microinfusion of TNFα and its antibody into locus coeruleus modifies nerve injury induced thermal hyperalgesia and mechanical allodynia

Introduction: Glial activation and secretion of cytokines at the spinal level is known as part of chronic pain pathogenesis. Although changes in TNFα at the supraspinal level are reported during chronic pain, its exact role and site of action remain to be elucidated. We investigated the effect of microinfusion of TNFα into the LC in a rat model of neuropathic pain. Methods: Male Wistar rats were cannulated in the LC. The cannula was connected to an Alzet mini-osmotic pump, which was filled by the drug (vehicle, TNFα or TNFα-antibody) and placed subcutaneously behind the neck. Twenty four-48 hours after cannulation, a chronic constriction injury (CCI) surgery was performed on the contralateral sciatic nerve. Hyperalgesia and allodynia symptoms were assessed 2, 4, 6, 8, 10 and 12 days after CCI. Results: Microinfusion of TNFα (100ng/day) into the LC significantly exacerbated the hyperalgesia in rat models of neuropathic pain on days 2 and 8 after CCI. On the other hand, microinfusion of TNFα antibody (250ng/day) decreased the symptoms of hyperalgesia on days 2, 4, 6, 8, 10 and 14. TNFα antibody also significantly alleviated the CCIinduced allodynia. Conclusion: These data suggest that alterations of TNFα levels in the LC play a crucial role in the development and maintenance of neuropathic pain.