Nociceptive neuroendocrine negative feedback control of neurogenic inflammation activated by capsaicin in the rat paw: role of the adrenal medulla

1. Recently we have found that inhibition of bradykinin-induced synovial pl asma extravasation by transcutaneous electrical stimulation at strengths wh ich excite unmyelinated afferent axons is mediated by the hypothalamo-pitui tary-adrenal axis. 2. Here we tested whether stimulation of nociceptors in the rat paw by intr adermally injected capsaicin inhibits bradykinin-induced synovial plasma ex travasation and whether this inhibition is mediated by the hypothalamo-pitu itary-adrenal or sympatho-adrenal axis. Furthermore, we tested whether inhi bition of bradykinin-induced plasma extravasation generated by intraperiton eally injected capsaicin, which preferentially excites visceral afferents, is mediated by the hypothalamo-pituitary-adrenal or sympatho-adrenal axis. We used normal rats, subdiaphragmatically vagotomized rats, rats with dener vated adrenal medullae and rats with acutely transected spinal cords at the segmental levels T-1/T-2 or T-12/L-1. 3. Injection of capsaicin into the plantar or palmar surface of the paws pr oduced a depression of bradykinin-induced plasma extravasation. The inhibit ion elicited from the forepaw was larger than that from the hindpaw. 4. The inhibition of bradykinin-induced plasma extravasation elicited from both paws was potentiated by subdiaphragmatic vagotomy. 5. Denervation of the adrenal medullae abolished the inhibitory effect of i ntradermal capsaicin in vagus-intact and in vagotomized animals. 6. after spinalization at the segmental Level T-1/T-2, capsaicin injected i nto the forepaw did not depress bradykinin-induced plasma extravasation eit her in vagus-intact or in vagotomized animals. Capsaicin injected into the hindpaw in these spinalized animals produced a small depression. After spin alization at the segmental level T-12/L-1 no depression was produced by cap saicin injected into the hindpaw. 7. Depression of bradykinin-induced plasma extravasation generated by intra peritoneal injection of capsaicin in vagus-intact and in vagotomized animal s was also abolished or attenuated after denervation of the adrenal medulla e. This shows that this depression was also largely dependent on the activa tion of the sympatho-adrenal system. 8. We conclude that depression of bradykinin-induced plasma extravasation d uring stimulation of nociceptors by capsaicin is mediated predominantly by the sympathoadrenal pathway. This finding differs from the inhibitory mecha nism of depression of bradykinin-induced plasma extravasation generated by cutaneous electrical stimulation, which is mediated by the hypothalamo-pitu itary-adrenal axis.