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HCN通道在神经病理性疼痛中的作用研究进展
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Abstract:
神经病理性疼痛(Neuropathic pain, NP)是一种常见且难治的慢性疼痛，由躯体感觉系统的损伤或疾病引起，其产生和维持可能与神经损伤后引起的外周和中枢敏化有关。NP严重影响患者的正常生活，且目前临床上缺乏治疗NP的有效方法。尽管NP发病的机制尚未完全阐明，但研究表明超极化激活的环核苷酸阳离子(Hyperpolarization activates cyclic nucleotide-gated, HCN)通道参与NP的病理生理过程；HCN通道可通过多巴胺D1受体、cAMP-PKA、α2受体、5-HT7受体、CaMKII/CREB、mTORC1等信号通路调节NP的敏感化。因此HCN通道有望成为靶向干预治疗NP的药物靶点。本文将重点阐述HCN通道在NP中的作用及其细胞分子机制，旨在为NP治疗药物的研发提供理论依据和新的策略。
Neuropathic pain (NP) caused by damage or disease of the somatosensory system is a common and refractory chronic pain. The mechanisms involved in induction and maintenance of NP have been associated with peripheral and central sensitization after nerve injury. There is no effective clinical treatment for NP at present and NP seriously affects the normal life of patients. The mechanisms underlying NP have not been fully elucidated, but the studies suggest that hyperpolarization activates cyclic nucleotide-gated (HCN) channel is involved in the path physiological process of NP. HCN channel modulates the sensitization of NP through the D1 receptor, cAMP-PKA, α2 receptor, 5-HT7 receptor, CaMKII/CREB and mTORC1 signaling pathways. This review focuses on the molecular and cellular mechanisms of the effect of HCN channels on NP, which may provide theoretical basis and new strategies for HCN channels as potential drug targets for targeted intervention therapy of NP.
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