Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain
Dan-Yang Li
Shao-Jie Gao
Jia Sun
Long-Qing Zhang
Jia-Yi Wu
Fan-He Song
Dai-Qiang Liu
Ya-Qun Zhou
Wei Mei
Department of Anesthesiology and Pain Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei Province,China
摘要：Nitric oxide(NO)/cyclic guanosine 3',5'-monophosphate(cGMP)signaling has been shown to act as a mediator involved in pain transmission and processing.In this review,we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain,including neuropathic pain,bone cancer pain,inflammatory pain,and morphine tolerance.The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase,which leads to subsequent production of cGMP.cGMP then activates cGMP-dependent protein kinase(PKG),resulting in the activation of multiple targets such as the opening of ATP-sensitive K+channels.The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules,as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain.In dorsal root ganglion neurons,natriuretic peptide binds to particulate guanylyl cyclase,generating and further activating the cGMP/PKG pathway,and it also contributes to the development of chronic pain.Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models.Notably the NO/cGMP signaling pathway induces expression of downstream effectors,exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain.These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain,and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.
机标关键词：pathwaycgmpoxidetreatchronicnitricpainsignaling
论文发表日期：2023-05-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 996-1003 )
英文信息