BRADYKININ-INDUCED SENSITIZATION OF AFFERENT NEURONS IN THE RAT PAW

Determination of the thermal nociceptive threshold in the rat hind paw was used to investigate the participation of postganglionic sympathet ic neurons and of capsaicin-sensitive afferent neurons to bradykinin-i nduced thermal hyperaesthesia. Intraplantar injection of 0.5 mu g brad ykinin or of 0.3 mu g prostaglandin E(2) significantly lowered paw wit hdrawal latencies, whereas injection of [des-Arg(9)]bradykinin was ine ffective. The B-2 receptor antagonist HOE 140 (0.1 mg/kg) prevented br adykinin- but not prostaglandin E(2)-induced thermal hyperaesthesia. W hile morphine (1 mg/kg) antagonized the effect of bradykinin and prost aglandin E(2), indomethacin (10 mg/kg) reduced only bradykinin-induced sensitization. Although this can be taken as indication that bradykin in-induced sensitization of heat-sensitive fibres is mainly mediated v ia local prostanoid formation, we failed to obtain evidence for an inv olvement of sympathetic postganglionic fibres in this process: chemica l sympathectomy, which lowered the tissue concentration of noradrenali ne by more than 90%, did not influence the ability of bradykinin to in duce a decrease in thermal nociceptive threshold. The target of bradyk inin/prostaglandin E(2) action seemed to be capsaicin-sensitive affere nts, since in rats which had been treated with capsaicin to destroy th is group of afferents, both substances were completely ineffective in producing sensitization. We suggest therefore that in the rat paw, bra dykinin, independently from sympathetic postganglionic neurons, lowers the thermal nociceptive threshold mainly via B-2 receptor-mediated fo rmation of cyclo-oxygenase products which, in turn, act exclusively on capsaicin-sensitive afferent neurons.