Mid-axonal tumor necrosis factor-alpha induces ectopic activity in a subset of slowly conducting cutaneous and deep afferent neurons.

After injuries to the musculoskeletal system, peripheral nerve axons are exposed to numerous inflammatory mediators, including tumor necrosis factor-alpha (TNF). Exposure of sensory axons to TNF can cause behavioral hypersensitivity in the peripheral innervation territory of the affected axons. The hypothesis that TNF activates nociceptor axons was tested by using teased fiber techniques in the rat. Recordings were made of single nociceptors innervating both deep and cutaneous receptive fields supplied by the sciatic nerve. The axons proximal to the receptive field were exposed to ascending concentrations of TNF (0.01 to 1 ng/mL). In 21% of cutaneous and 9% of deep neurons, TNF rapidly evoked a transient response. There was no difference between deep and cutaneous nociceptors in the incidence of TNF responses. The majority of neurons responded to TNF injected into their receptive fields. Our data support that TNF can induce ectopic electrogenesis in a minority of nociceptor axons that innervate both deep and cutaneous tissues. This activity may correlate to the human perception of radiating pain that often accompanies neuritis.