Interleukin-2 activates a sub-population of cutaneous C-fibre polymodal nociceptors in the rat hairy skin.
We have investigated the effects of interleukin-2 on identified cutaneous C- and A delta- fibre nociceptors in an in vivo rat saphenous nerve preparation. A fraction of C-polymodal (33%), A delta- (22%) and C- (7.5%) mechanical nociceptors were activated by intradermal injection of interleukin-2. For C-fibre polymodal nociceptors, concentration thresholds were < or = 0.12 unit/3 microliters and the percentage of interleukin-2-activated nociceptors did not increase with concentrations above 0.06 unit/3 microliters. Responses were dose-dependent and characterized by potent tachyphylaxis for subsequent injections of the same dose. C-fibre polymodal nociceptors activated by interleukin-2 were also activated by subsequent chemical stimuli as follows: 81% were activated by histamine (300 ng/3 microliters), 87% by bradykinin (75 ng/3 microliters), 100% by topical acetic acid and 87% by capsaicin (3 micrograms/3 microliters). In contrast, C-fibre polymodal nociceptors that could not be activated by interleukin-2 responded less frequently to histamine (17%) and bradykinin (24%) but were generally activated by noxious chemicals, including acetic acid (82%) and capsaicin (70%). In conclusion, this study demonstrates that interleukin-2 is a potent activator of a discrete population of cutaneous C-polymodal nociceptors, which are chemosensitive to endogenous inflammatory mediators. The fact that these nociceptors respond to a variety of endogenous mediators is consistent with the concept of multiple humoral mechanisms of itch and, consequently, the difficulties in reducing itch associated with inflammation.
Martin
H A
HA
University of Newcastle upon Tyne, Division of Neurobiology, School of Neurosciences, Medical School, U.K.
Murphy
P R
PR
D000818:Animals; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation*
D007376:Interleukin-2