BACKGROUND: Following musculoskeletal injuries, axons are exposed to tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. Exposure of axons to TNF-alpha and complete Freund's adjuvant (CFA) can cause hyperalgesia or allodynia in the distribution of the affected axons. The hypothesis that TNF-alpha, inflammatory mediators, and inflammation secondary to CFA activate nociceptor axons was tested using teased fiber techniques in the rat. METHODS: Electrophysiologic recordings were made from single nociceptors innervating both deep and cutaneous receptive fields (RF) supplied by the sciatic nerve. The axons proximal to the RF were exposed to either TNF-alpha, a mixture of inflammatory mediators (histamine, serotonin, bradykinin, and prostaglandin), or CFA. RESULTS: In a minority of nociceptors (15%), TNF-alpha rapidly evoked a response that was dose- dependent and transient. There was no difference between deep and cutaneous nociceptors in the incidence of TNF-alpha responses. The majority of neurons responded to TNF-alpha injected into their RFs. No neurons responded to axonal application of either the mixed inflammatory mediators or CFA. CONCLUSIONS: Our data supports that TNF-alpha can induce ectopic electrogenesis in nociceptor axons that innervate both deep and cutaneous tissues. This activity may correlate to the human perception of radicular pain that is often associated with neuritis.
Animals ; Axons* ; Bradykinin ; Freund's Adjuvant ; Humans ; Hyperalgesia ; Incidence ; Inflammation ; Neuritis ; Neurons ; Nociceptors ; Rats ; Sciatic Nerve ; Serotonin ; Tumor Necrosis Factor-alpha*