Role of NGF TrkA signaling in pain and an insight into the TrkA inhibitors as analgetics

TrkA is the receptor tyrosine kinase for nerve growth factor(NGF) and binds NGF selectively.Apart from the pivotal role in the process of neuronal survival,differentiation and axon growth,NGF and its TrkA receptor also play a crucial role in the occurrence and maintenance of pain.Studies have shown that blocking the NGF-TrkA axis can significantly relieve pain and hyperalgesia.Antagonizing NGF together with its signaling is,therefore,a promising therapeutic strategy.Indeed,there are at least three major pharmacologic strategies that target on NGF-TrkA signaling for the treatment of pain:sequestration of NGF or inhibiting its binding to TrkA;antagonizing TrkA so as to block NGF from binding to TrkA;and blocking TrkA kinase activity.The application of TrkA inhibitors as analgetics might provide a novel treatment for chronic pain.In this paper,we review the research development of Trk receptor in pain and Trk A inhabitor.