BRADYKININ POTENTIATES THE CHEMORESPONSIVENESS OF RAT CUTANEOUS C-FIBER POLYMODAL NOCICEPTORS TO INTERLEUKIN-2

We have recently reported that IL-2 activates a third of cutaneous C-f ibre polymodal nociceptors. Responses were dose-dependent and concentr ation threshold was below 1.2 U/3 mu l. Potent tachyphylaxis character ized the response to subsequent injections of the same dose. These noc iceptors were also activated by histamine and bradykinin. However, the cross-reactivity between inflammatory mediators was not assessed due to experimental limitations. Nevertheless, we found in preliminary stu dies that BK enhanced the responsiveness of polymodal nociceptors to I L-2 by reversing IL-2-induced tachyphylaxis and increasing response ma gnitude. The fact that BK potentiated the responsiveness of nociceptor s to a chemical stimulus was unexpected and needed further investigati on. In the present study, 40 cutaneous C-fibre polymodal nociceptors w ere isolated in 26 rat saphenous nerve preparations. Nociceptors were identified by their conduction velocity and response thresholds to ele ctrical, mechanical and thermal stimuli. Two series of experiments wer e conducted: in the first series of experiments, IL-2 (1.2 U/3 mu l) w as injected twice prior to BK (150 ng/3 mu l) and injected again twice after BK. In the second series of experiments, BK preceded the two in jections of IL-2. In the first series of experiments, responses to IL- 2 were increased by 55% after BK and this difference was statistically significant in a paired-sample t-test (P<0.02). In the second series of experiments, units responded to IL-2 with a vigorous and irregular (bursting) sustained discharge (255 +/- 35 action potentials/300 s) an d no tachyphylaxis appeared to the second IL-2 injection. In addition, potent thermal sensitization occurred after BK. Possible cellular and sub-cellular mechanisms of BK-induced potentiation to IL-2 are discus sed. We conclude that BK enhances the responsiveness of cutaneous C-fi bre polymodal nociceptors to IL-2, which may explain the occurrence of pruritus in the healing process of inflamed skin.