Role of nerve growth factor in pain.

Nerve growth factor (NGF) was first identified as a substance that is essential for the development of nociceptive primary neurons and later found to have a role in inflammatory hyperalgesia in adults. Involvement of NGF in conditions with no apparent inflammatory signs has also been demonstrated. In this review we look at the hyperalgesic effects of exogenously injected NGF into different tissues, both human and animal, with special emphasis on the time course of these effects. The roles of NGF in inflammatory and neuropathic conditions as well as cancer pain are then reviewed. The role of NGF in delayed onset muscle soreness is described in more detail than its other roles based on the authors' recent observations. Acute effects are considered to be peripherally mediated, and accordingly, sensitization of nociceptors by NGF to heat and mechanical stimulation has been reported. Changes in the conductive properties of axons have also been reported. The intracellular mechanisms so far proposed for heat sensitization are direct phosphorylation and membrane trafficking of TRPV1 by TrkA. Little investigation has been done on the mechanism of mechanical sensitization, and it is still unclear whether mechanisms similar to those for heat sensitization work in mechanical sensitization. Long-lasting sensitizing effects are mediated both by changed expression of neuropeptides and ion channels (Na channels, ASIC, TRPV1) in primary afferents and by spinal NMDA receptors. Therapeutic perspectives are briefly discussed at the end of the chapter.