| Neuropathic pain is a chronic pain syndrome associated with drug, injury or disease-induced destruction of sensory afferent fibers of the dorsal root ganglia (DRG). Although the exact underlying mechanisms involved in its pathogenesis is not known, pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), is recognized as a principle modulator in the early development of neuropathic pain through inducing sensory neuronal apoptosis via the mitogen-activated protein kinases (MAPKs) pathway. The results of this study demonstrate a transient upregulation of TNF-alpha expression within bilateral DRG following unilateral sciatic nerve axotomy. Peak TNF-alpha expression is shown to occur within the first 7 days post-axotomy, which normalizes to baseline level by day 14. During the first week post-axotomy, the identified transient upregulation of TNF-alpha is associated with a switch in source production from satellite cells to sensory neurons. Our results indicate that peripheral nerve injury triggers the integral production of TNF-alpha within the DRG representing a novel mechanism for axotomy-induced neuropathic pain. |
