Regulation and function of spinal and peripheral neuronal B1 bradykinin receptors in inflammatory mechanical hyperalgesia

Activation of either B-1 or B-2 bradykinin receptors by kinins released from damaged tissues contributes to the development and maintenance of inflammatory hyperalgesia. Whereas B-2 agonists activate sensory neurones directly, B-1 agonists were thought only to have indirect actions on sensory neurones. The recent discovery of constitutive B-1 receptor expression in the rat nervous system lead us to re-investigate the role of neuronal B-1 receptors in inflammatory hyperalgesia. Therefore we have examined B-1 bradykinin receptor regulation in rat dorsal root ganglia in a model of inflammatory hyperalgesia, and correlated it with hyperalgesic behaviour. Twenty-four hours after injection of Freund's complete adjuvant into one hindpaw, there was a significant increase in B-1 protein expression (measured by immunohistochemistry) in both ipsilateral and contralateral dorsal root ganglion neurones. whereas axotomy resulted in reduction of B-1 protein in ipsilateral dorsal root ganglia In behavioural experiments, the B-1 artagonist desArg(10)HOE140, administered by either intrathecal or systemic routes. attenuated Freund's complete adjuvant-induced mechanical hyperalgesia in the inflamed paw, but did not affect mechanical allodynia. The B-1 agonist, desArg(9)BK, did not affect paw withdrawal thresholds in naive rats following intraplantar administration into the paw, whilst intrathecal administration elicited mechanical hyperalgesia. However, after Freund's complete adjuvant-induced inflammation, desArg(9)BK caused a marked mechanical hyperalgesia, by either route, of the contralateral, uninflamed hindpaw, correlating with the observed contralateral and ipsilateral increases in receptor levels. Our results suggest a functional role for B-1 receptors expressed both in the periphery and in the spinal cord, in mechanical hyperalgesia during inflammation. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.