Nerve growth factor regulates nociception in human health and disease

Abstract

In this review, evidence is marshalled for the hypothesis that nerve growth factor (NGF) regulates nociception in human health and disease. The data from humans complement the studies of NGF in animal inflammatory pain models described elsewhere in this issue. An attempt is made to unify the role of NGF in inflammatory and neuropathic hyperalgesia. Although largely speculative at this stage, human conditions are discussed that may present with pain related to alterations of NGF activity—these may provide suitable models for the study of mechanisms of NGF and pain in humans, and new NGF-related prophylaxis and therapies. The “hyperalgesic” conditions include arthritis, some small fibre neuropathies, painful hypertrophic scars, sunburn, urinary bladder pain, migraine and vascular head pain. The “hypoalgesic” group includes leprosy neuropathy. Other conditions, including the major neuropathies that occur after trauma and diabetes, are more complicated and may display different NGF-related features during their development. A neurotrophic factor may be defined as an endogenous substance that plays a role in the development, maintenance or regeneration of the nervous system. Trophic factors act via their highaffinity receptors on specific nerve cells to influence their survival and gene expression. Recent studies have identified a number of neurotrophic factors which play specific roles in the development, maintenance and regeneration of subpopulations of peripheral nerve fibres [24, 39]. The classic neurotrophic factor, NGF, is a protein normally produced by cells in the target organs, such as skin, blood vessels and the bladder; the NGF is secreted, then taken up by sympathetic and small sensory fibres via a high-affinity receptor (trkA), and transported retrogradely to the cell body [2]. In adults,GF is necessary fo r the survivalf sympathetic fibres, and for phenotypic properties of small sensory fibres, such as expression of neuropeptide substance P and capsaicin sensitivity [40, 43, 63]. NGF also has paracrine actions—for example, it