Neurotrophins, nociceptors, and pain

It is now well established that neurotrophins play a crucial role in the de velopment of the nervous system. However, there is increasing evidence that the function of neurotrophins persists throughout adulthood. The broad sco pe of neurotrophin action is well documented in the case of nerve growth fa ctor (NGF) and its effect on nociceptors and nociception. Here, we review t he evidence for these multiple roles for NGF. Two manipulations influencing NGF levels are discussed in detail. The first involves the use of transgen ic mice that overexpress or underexpress neurotrophins. A second strategy i nvolves administration of NGF or its antibody in vivo to increase or decrea se its level. During prenatal development, NGF is required for survival of nociceptors. In the early postnatal period, NGF is required for expression of the appropriate nociceptor phenotype. In adults, NGF acts as an importan t intermediate in inflammatory pain, contributing to both peripheral and ce ntral sensitization. The sensitization of peripheral nociceptors can be ver y rapid and can involve non-neural cells such as mast cells, neutrophils, f ibroblasts, and macrophages. Recent evidence indicates that other neurotrop hins also play key supporting roles in the development of nociceptors (e.g. , NT-3) and in inflammatory pain (e.g., BDNF, NT-4/5). Furthermore, molecul es from other superfamilies (e.g., GDNF) also are required to assure surviv al of certain classes of nociceptors. The diverse effects of neurotrophins on nociceptive processing emphasize their broad importance in the developme nt and function of the nervous system. Microse Res Tech 45:252-261, 1999. a (C) 1999 Wiley-Liss, Inc.