Nociceptive and inflammatory effects of subcutaneous TNFalpha.
Tumor necrosis factor alpha (TNF) is a potent pro-inflammatory cytokine that produces pain and hyperalgesia following injection. Its algesic effects are due to sensitizing actions on nociceptive primary afferents and to the upregulation of other pro-inflammatory and algesic proteins. In anesthetized rats, we investigated the effect of subcutaneously injected TNF on background 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 in 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 Abeta mechanoreceptive fibers. In addition, TNF evoked ongoing activity in 14% of C nociceptors and caused significant and dose-related increases in vascular permeability in glabrous skin. Our data suggest that TNF released during disease or after tissue injury participates in the generation of hyperalgesia and inflammation.
Junger
H
H
Department of Anesthesiology, University of California at San Diego, 9500 Gilman Drive, San Diego, USA.
Sorkin
L S
LS
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced* / Q000523:psychology; D007279:Injections, Subcutaneous; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D010146:Pain / Q000139:chemically induced* / Q000523:psychology; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha