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 sympathetic neurons and of capsaicin-sensitive afferent neurons to bradykinin-induced thermal hyperaesthesia. Intraplantar injection of 0.5 microgram bradykinin or of 0.3 microgram prostaglandin E2 significantly lowered paw withdrawal latencies, whereas injection of [des-Arg9]bradykinin was ineffective. The B-2 receptor antagonist HOE 140 (0.1 mg/kg) prevented bradykinin- but not prostaglandin E2-induced thermal hyperaesthesia. While morphine (1 mg/kg) antagonized the effect of bradykinin and prostaglandin E2, indomethacin (10 mg/kg) reduced only bradykinin-induced sensitization. Although this can be taken as indication that bradykinin-induced sensitization of heat-sensitive fibres is mainly mediated via local prostanoid formation, we failed to obtain evidence for an involvement of sympathetic postganglionic fibres in this process: chemical sympathectomy, which lowered the tissue concentration of noradrenaline by more than 90%, did not influence the ability of bradykinin to induce a decrease in thermal nociceptive threshold. The target of bradykinin/prostaglandin E2 action seemed to be capsaicin-sensitive afferents, since in rats which had been treated with capsaicin to destroy this group of afferents, both substances were completely ineffective in producing sensitization. We suggest therefore that in the rat paw, bradykinin, independently from sympathetic postganglionic neurons, lowers the thermal nociceptive threshold mainly via B-2 receptor-mediated formation of cyclo-oxygenase products which, in turn, act exclusively on capsaicin-sensitive afferent neurons.