NGF as a mediator of inflammatory pain.
The chapter reviews some of recent evidence which suggests that one neurotrophin, nerve growth factor (NGF), is a peripherally produced mediator of some persistent pain states, notably those associated with inflammation. The evidence for this proposal is as follows. 1. The endogenous production of NGF regulates the sensitivity of nociceptive systems. Behavioural and electrophysiological studies have shown that sequestration of constitutively produced NGF leads to decrease nociceptor sensitivity. 2. In a wide variety of experimental inflammatory conditions 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 such 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 activate and sensitize fine calibre sensory neurons. 5. In a number of animal models, much of the hyperalgesia associated with experimental inflammation is blocked by pharmacological "antagonism' of NGF. The mechanisms by which NGF up-regulation in inflamed tissues might lead to sensory abnormalities is also discussed. In particular, evidence is reviewed which suggests that increased NGF levels leads to both peripheral sensitization of nociceptors and central sensitization of dorsal horn neurons responding to noxious stimuli.
McMahon
S B
SB
Department of Physiology, St Thomas's Hospital Medical School (UMDS), London, UK.
D000818:Animals; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced; D018836:Inflammation Mediators / Q000502:physiology*; D008959:Models, Neurological; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000209:etiology*; D015854:Up-Regulation
D018836:Inflammation Mediators; D009414:Nerve Growth Factors