ENDOGENOUS NERVE GROWTH-FACTOR REGULATES THE SENSITIVITY OF NOCICEPTORS IN THE ADULT-RAT

Nerve growth factor (NGF) has a well characterized role in the develop ment of the nervous system and there is evidence that it interacts wit h nociceptive primary afferent fibres, Here we applied a synthetic tyr osine kinase A IgG (trkA-IgG) fusion molecule for 10-12 days to the in nervation territory of the purely cutaneous saphenous nerve in order t o bind, and thereby neutralize endogenous NGF in adult Fats. Using neu rophysiological analysis of 152 nociceptors we now show that sequestra tion of NGF results in specific changes of their receptive field prope rties. The percentage of nociceptors responding to heat dropped signif icantly from a normal 57% to 32%. This was accompanied by a rightward shift and a reduced slope of the stimulus response function relating t he intracutaneous temperature to the neural response. The number of no ciceptors responding to application of bradykinin was also significant ly reduced from a normal of 28% to 8%, In contrast, the threshold for mechanical stimuli and the response to suprathreshold stimuli remained unaltered, as did the percentage of nociceptors responding to noxious cold. The reduced sensitivity of primary afferent nociceptors was acc ompanied by a reduction in the innervation density of the epidermis by 44% as assessed with quantitative immunocytochemical analysis of the panaxonal marker PGP 9.5. This demonstrates that endogenous NGF in the adult specifically modulates the terminal arborization of unmyelinate d fibres and the sensitivity of primary afferent nociceptors to therma l and chemical stimuli in vivo.