Nerve growth factor (NGF) is thought of as a targetderived factor responsible for the survival and maintaining the phenoOrpe of specific sets of peripheral and central neurons during development and maturation. Recently, using physiological techniques, we have shown that specific functional b'pes of nociceptive sensory neurons require NGF, first for survival during development in utero and then for their normal phenob, pic development (but not survival) in the early postnatal period. In adulthood, the physiological role of NGF changes dramatically and here it may serve as a link between inflammation and hyperalgesia. Despite apparent changes in NGF's mode of action as the animal matures, it always interacts specifically with nociceptive sensory neurons.

The neurotrophic hypothesis states that, during development, neurons are critically dependent for survival on target-derived factors. The presence of limiting amounts of such factors ensures that only a proportion of neurons survive naturally occurring cell death and that the appropriate innervation density of the target is attained. Nerve growth factor (NGF) is the prototypical neurotrophic factor and is a survival factor for both sympathetic and sensory neurons during development 1. Many sympathetic neurons continue to depend on NGF for survival into adulthood, whereas sensory neurons cease to rely on this molecule in the postnatal period 2~. Furthermore, it appears that at no point during development are all sensory neurons dependent on NGF for survival. Indeed, the number of neurons that need NGF for survival gets smaller as development proceeds (see Box 1). This change in dependence on NGF for survival occurs despite the fact that many smalldiameter peptide-containing sensory neurons in the adult have high-affinity NGF receptors and retrogradely transport NGF from their target tissues 5'6. This suggests that NGF has a physiological role in the adult that is distinct from that in development. Several lines of evidence have indicated that the action of NGF on sensory neurons might be directed to specific functional groups of nociceptive neurons. For example, small sensory neurons containing neuropeptides, such as substance P, do not survive NGF deprivation during development (see Box 1); and in adults, the levels of these peptides are downregulated after NGF deprivation 7'8. High-affinity NGF receptors are present primarily on this same population of neuropeptide-containing neurons 6. Conversely, large cells devoid of peptides do not require NGF for survival and do not have high-affinity NGF receptors 6'9'1. It is widely assumed that peptidecontaining neurons are nociceptive sensory neurons with unmyelinated or thinly myelinated axons 13 (see Box 2). The fact that they are susceptible to NGF deprivation suggests that NGF regulates a functional group of sensory neurons. In addition, the sensitivity of adult sensory neurons to capsaicin, a compound