Sensitisation 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 adult rat urinary bladder. Single A delta and C fibres were dissected from the L6 or S1 dorsal roots of urethane anaesthetized rats. The stimulus-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 micrograms/ml solution of human recombinant NGF in 10% DMSO. In the control state, and after filling with 10% DMSO, the myelinated and about one-half of the unmyelinated afferents were mechanosensitive with pressure thresholds in the innocuous range and responsiveness extending into the supra physiological, presumed noxious range. The remaining one-half of unmyelinated afferents showed no mechanosensitivity. After filling with NGF, the large majority of units, both myelinated and unmyelinated, sensitised, evidenced by the development of ongoing activity and a leftward shift of stimulus-response functions. Some of the initially nonmechanosensitive units developed a novel mechanosensitivity. The sensitisation began within 30 min of exposure to NGF, and persisted for the period studied (up to the 3 h). In separate experiments, intravesical NGF at concentrations greater than 1 microgram/ml was found to elicit a dose-dependent extravasation of Evan's blue into the bladder. These data support the notion that NGF may be an endogenous mediator in some persistent pain states.