Neurotrophins, nociceptors, and pain

It is now well established that neurotrophins play a crucial role in the development of the nervous system. However, there is increasing evidence that the function of neurotrophins persists throughout adulthood. The broad scope of neurotrophin action is well documented in the case of nerve growth factor (NGF) and its effect on nociceptors and nociception. Here, we review the evidence for these multiple roles for NGF. Two manipulations influencing NGF levels are discussed in detail. The first involves the use of transgenic mice that overexpress or underexpress neurotrophins. A second strategy involves administration of NGF or its antibody in vivo to increase or decrease 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 important intermediate in inflammatory pain, contributing to both peripheral and central sensitization. The sensitization of peripheral nociceptors can be very rapid and can involve non-neural cells such as mast cells, neutrophils, fibroblasts, and macrophages. Recent evidence indicates that other neurotrophins 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, molecules from other superfamilies (e.g., GDNF) also are required to assure survival of certain classes of nociceptors. The diverse effects of neurotrophins on nociceptive processing emphasize their broad importance in the development and function of the nervous system.