Nociceptive and inflammatory effects of subcutaneous TNF alpha

Tumor necrosis factor alpha (TNF) is a potent pro-inflammatory cytokine tha t produces pain and hyperalgesia following injection. Its algesic effects a re due to sensitizing actions on nociceptive primary afferents and to the u pregulation of other pro-inflammatory and algesic proteins. In anesthetized rats, we investigated the effect of subcutaneously injected TNF on backgro und activity and mechanical sensitivity of C nociceptors of the sural nerve , as well as its effects on cutaneous plasma extravasation. TNF sensitized C nociceptors dose-dependently; the optimal dose (5 ng) lowered threshold i n 66.7% of the tested fibers. This sensitization occurred within 30 min and could last for 2 or more hours. Injected TNF had no effect on A beta mecha noreceptive fibers. In addition, TNF evoked ongoing activity in 14% of C no ciceptors and caused significant and dose-related increases in vascular per meability in glabrous skin. Our data suggest that TNF released during disea se or after tissue injury participates in the generation of hyperalgesia an d inflammation. (C) 2000 International Association for the Study of Pain. P ublished by Elsevier Science B.V. All rights reserved.