SENSITIZATION OF VISCERAL AFFERENTS BY NERVE GROWTH-FACTOR IN THE ADULT-RAT

Since there is growing evidence that nerve growth factor (NGF) acts as a mediator of persistent pain states, here we have studied its acute effects on the properties of primary afferent neurones innervating adu lt rat urinary bladder. Single A delta and C fibres were dissected fro m the L6 or S1 dorsal roots of urethane anaesthetized rats. The stimul us-response function of these afferents was evaluated with a series of isotonic distensions of the bladder (0-60 cm H2O). The afferents were then studied after filling the bladder with a vehicle solution of 10% DMSO for 30 min, and then again after filling the bladder with a 10 m u g/ml solution of human recombinant NGF in 10% DMSO. In the control s tate, and after filling with 10% DMSO, the myelinated and about one-ha lf of the unmyelinated afferents were mechanosensitive with pressure t hresholds in the innocuous range and responsiveness extending into the supra physiological, presumed noxious range. The remaining one-half o f unmyelinated afferents showed no mechanosensitivity. After filling w ith NGF, the large majority of units, both myelinated and unmyelinated , sensitised, evidenced by the development of ongoing activity and a l eftward shift of stimulus-response functions. Some of the initially no n-mechanosensitive units developed a novel mechanosensitivity. The sen sitisation began within 30 min of exposure to NGF, and persisted for t he period studied (up to the 3 h). In separate experiments, intravesic al NGF at concentrations greater than 1 mu g/ml was found to elicit a dose-dependent extravasation of Evan's blue into the bladder. These da ta support the notion that NGF may be an endogenous mediator in some p ersistent pain states.