Cyclic nucleotide signaling in sensory neuron hyperexcitability and chronic pain after nerve injury.
Cyclic nucleotide signaling in sensory neuron hyperexcitability and chronic pain after nerve injury.
复制标题
感觉神经元过度兴奋和神经损伤后慢性疼痛中的环核苷酸信号传导
DOI：
10.1016/j.ynpai.2019.100028
复制
发表时间：
2019-08-01
期刊：
影响因子：
--
通讯作者：
Song, Xue-Jun
中科院分区：
文献类型：
--
作者：
Li, Ze-Hua;Cui, Dong;Song, Xue-Jun
环核苷酸信号通路包括cAMP-PKA和cGMP-PKG通路，在调节细胞生长、代谢和许多其他细胞内过程中发挥着重要作用。近年来，越来越多的研究揭示了cAMP和cGMP在神经系统中的作用。cAMP和cGMP信号传导介导由不同形式的损伤和应激诱导的慢性疼痛。本文就cAMP-PKA和cGMP-PKG信号通路在神经损伤后慢性疼痛发病机制中的作用作一综述。此外，背根神经节（DRG）神经元的急性分离和慢性压迫，分别导致神经过度兴奋可能通过PAR 2激活依赖性激活cAMP-PKA通路。临床上，放射治疗至少部分通过抑制癌细胞诱导的cAMP-PKA通路的激活而有效缓解骨癌疼痛。环核苷酸信号传导在神经性和炎性疼痛中的作用也见于许多其他动物模型中，并且涉及许多促伤害性机制，包括超极化激活的环核苷酸（HCN）调节的离子通道和由cAMP直接激活的交换蛋白（EPAC）的激活。深入了解cAMP和cGMP信号通路在慢性疼痛发病机制中的作用，对慢性疼痛的治疗具有重要的理论意义和临床价值。
The cyclic nucleotide signaling, including cAMP-PKA and cGMP-PKG pathways, has been well known to play critical roles in regulating cellular growth, metabolism and many other intracellular processes. In recent years, more and more studies have uncovered the roles of cAMP and cGMP in the nervous system. The cAMP and cGMP signaling mediates chronic pain induced by different forms of injury and stress. Here we summarize the roles of cAMP-PKA and cGMP-PKG signaling pathways in the pathogenesis of chronic pain after nerve injury. In addition, acute dissociation and chronic compression of the dorsal root ganglion (DRG) neurons, respectively, leads to neural hyperexcitability possibly through PAR2 activation-dependent activation of cAMP-PKA pathway. Clinically, radiotherapy can effectively alleviate bone cancer pain at least partly through inhibiting the cancer cell-induced activation of cAMP-PKA pathway. Roles of cyclic nucleotide signaling in neuropathic and inflammatory pain are also seen in many other animal models and are involved in many pro-nociceptive mechanisms including the activation of hyperpolarization-activated cyclic nucleotide (HCN)-modulated ion channels and the exchange proteins directly activated by cAMP (EPAC). Further understanding the roles of cAMP and cGMP signaling in the pathogenesis of chronic pain is theoretically significant and clinically valuable for treatment of chronic pain.