NGF AS A MEDIATOR OF INFLAMMATORY PAIN

The chapter reviews some of recent evidence which suggests that one ne urotrophin, nerve growth factor (NGF), is a peripherally produced medi ator of some persistent pain states, notably those associated with inf lammation. The evidence for this proposal is as follows. 1. The endoge nous production of NGF regulates the sensitivity of nociceptive system s. Behavioural and electrophysiological studies have shown that seques tration of constitutively produced NGF leads to decrease nociceptor se nsitivity. 2. In a wide variety of experimental inflammatory condition s NGF levels are rapidly increased in the inflamed tissue. 3. The high -affinity NGF receptor, trkA, is selectively expressed by nociceptive sensory neurons particularly those containing sensory neuropeptides su ch as substance P and CGRP. 4. The systematic or local application of exogenous NGF produces a rapid and prolonged behavioural hyperalgesia in both animals and humans. Exogenous NGF has also been found to activ ate and sensitize fine calibre sensory neurons. 5. In a number of anim al models, much of the hyperalgesia associated with experimental infla mmation is blocked by pharmacological 'antagonism' of NGF. The mechani sms by which NGF up-regulation in inflamed tissues might lead to senso ry abnormalities is also discussed. In particular, evidence is reviewe d which suggests that increased NGF levels leads to both peripheral se nsitization of nociceptors and central sensitization of dorsal horn ne urons responding to noxious stimuli.