Vagotomy-induced enhancement of mechanical hyperalgesia in the rat is sympathoadrenal-mediated

We have recently shown that subdiaphragmatic vagotomy enhances bradykinin-induced hyperalgesic behavior and decreases baseline paw withdrawal threshold to mechanical stimulation of the hindpaw skin in rats by a peripheral mechanism. To elucidate the underlying mechanism, we studied whether lesions of efferent neuroendocrine pathways could prevent or reverse the potentiating effect of vagotomy. In groups of sham-vagotomized or vagotomized rats, we surgically removed or denervated the adrenal medulla. Bradykinin was injected intradermally into the skin of the dorsal surface of the rat hindpaw. Threshold of paw withdrawal to mechanical stimulation of the skin was measured. Vagotomy induced a decrease in mechanical baseline paw withdrawal threshold and enhancement of bradykinin-induced mechanical hyperalgesic behavior, both of which were maintained over the 5 week testing period. Adrenal enucleation or denervation of the adrenal gland by suprarenal ganglionectomy prevented vagotomy-induced decrease in baseline paw withdrawal threshold and enhancement of bradykinin-induced hyperalgesia. In animals that had a demonstrated decrease in baseline paw withdrawal threshold and enhancement of bradykinin-induced hyperalgesia 2 weeks after vagotomy, additional denervation of the adrenal medulla significantly reversed these effects over a 3 week period. These results imply that both the decrease in baseline paw withdrawal threshold and enhancement of bradykinin-induced hyperalgesic behavior after vagotomy are dependent on a hormonal signal released from the adrenal medulla and suggest a novel mechanism of sensitization of cutaneous nociceptors.