INTERLEUKIN-2 ACTIVATES A SUBPOPULATION OF CUTANEOUS C-FIBER POLYMODAL NOCICEPTORS IN THE RAT HAIRY SKIN

We have investigated the effects of interleukin-2 on identified cutane ous 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 o f interleukin-2. For C-fibre polymodal nociceptors, concentration thre sholds were less than or equal to 0.12 unit/3 mu l and the percentage of interleukin-2-activated nociceptors did not increase with concentra tions above 0.06 unit/3 mu l. Responses were dose-dependent and charac terized by potent tachyphylaxis for subsequent injections of the same dose. C-fibre polymodal nociceptors activated by interleukin-2 were al so activated by subsequent chemical stimuli as follows: 81% were activ ated by histamine (300 ng/3 mu l), 87% by bradykinin (75 ng/3 mu l), 1 00% by topical acetic acid and 87% by capsaicin (3 mu g/3 mu l). in co ntrast C-fibre polymodal nociceptors that could not be activated by in terleukin-2 responded less frequently to histamine (17%) and bradykini n (24%) but were generally activated by noxious chemicals, including a cetic acid (82%) and capsaicin (70%). In conclusion, this study demons trates that interleukin-2 is a potent activator of a discrete populati on of cutaneous C-polymodal nociceptors, which are chemosensitive to e ndogenous inflammatory mediators. The fact that these nociceptors resp ond to a variety of endogenous mediators is consistent with the concep t of multiple humoral mechanisms of itch and consequently, the difficu lties in reducing itch associated with inflammation.