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.
Dmitrieva
Natalia
N
Department of Physiology, St Thomas' Hospital Medical School (UMDS), Lambeth Palace Road,London, SE1 7EH,UK.
McMahon
Stephen B
SB
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005070:Evans Blue; D005260:Female; D006801:Humans; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D001743:Urinary Bladder / Q000294:innervation*
D009414:Nerve Growth Factors; D014677:Pharmaceutical Vehicles; D011994:Recombinant Proteins; D005070:Evans Blue; D004121:Dimethyl Sulfoxide