神经生长因子-TrkA信号通路在疼痛中的作用机制及TrkA抑制剂的研究进展

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

TrkA是神经生长因子(NGF)的受体酪氨酸激酶,选择性结合NGF,除了在神经系统多种神经元的生长发育、分化和轴突形成过程中起关键作用外,神经生长因子及其功能性受体TrkA在疼痛的产生及维持过程中也起了重要作用。研究证明,阻断NGF-TrkA信号可有效抑制疼痛及痛觉过敏。对于疼痛的治疗,目前主要有3种针对NGF-TrkA信号的药理学方法:隔绝或消除内源性NGF、拮抗TrkA受体以阻止其与NGF结合、阻断TrkA激酶活性。以TrkA受体为靶点,应用TrkA抑制剂阻断TrkA信号可为更好治疗疼痛提供新方法。本文就TrkA受体在疼痛中的作用以及TrkA抑制剂的研究进展作一综述。

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.