TUMOR-NECROSIS-FACTOR-ALPHA INDUCES ECTOPIC ACTIVITY IN NOCICEPTIVE PRIMARY AFFERENT-FIBERS

Tumour necrosis factor-alpha, a pro-inflammatory cytokine, is expresse d endoneurially following a variety of local and systemic pathophysiol ogical insults which give rise to pain. We administered tumour necrosi s factor-alpha to pentobarbital-anaesthetized rats, either topically a long a restricted portion of the sciatic nerve or injected subcutaneou sly within the distribution of the sural nerve. Single nociceptive pri mary afferent fibres were assessed for ectopic discharge and receptor sensitization. Low concentrations (0.001-0.01 ng/ml) of tumour necrosi s factor-alpha applied along the nerve elicited a dose-dependent, rapi d onset (1-3 min) increase in discharge; higher concentrations led to reduced firing rates. C-fibres developed higher mean firing frequencie s than A delta-fibres. Bursting frequency in both fibre types reached several (6) Hz. No change in mechanical threshold was observed. Intrad ermal injection (50 pg in 50 mu l) led to ectopic discharge and a decr ease in mechanical threshold; these effects developed at different rat es, suggesting multiple actions of the cytokine. Our data suggest that acute application of tumour necrosis factor-alpha to the axon can lea d to aberrant electrophysiologic activity independent of peripheral re ceptor involvement. This low level of ectopic firing of nociceptive ax ons may produce wind-up in dorsal horn neurons or may, by itself, be i nterpreted as pain. (C) 1997 IBRO. Published by Elsevier Science Ltd.