Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun 130033, Jilin Province, China.
Department of Paediatrics, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
Rev Neurosci. 2019 Jul 26;30(6):639-649. doi: 10.1515/revneuro-2018-0094.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are activated during hyperpolarization, and there is an inward flow of current, which is termed as hyperpolarization-activated current, Ih. Initially, these channels were identified on the pacemaker cells of the heart. Nowadays, these are identified on different regions of the nervous system, including peripheral nerves, dorsal root ganglia, dorsal horns, and different parts of the brain. There are four different types of HCN channels (HCN1-HCN4); however, HCN1 and HCN2 are more prominent. A large number of studies have shown that peripheral nerve injury increases the amplitude of Ih current in the neurons of the spinal cord and the brain. Moreover, there is an increase in the expression of HCN1 and HCN2 protein channels in peripheral axons and the spinal cord and brain regions in experimental models of nerve injury. Studies have also documented the pain-attenuating actions of selective HCN inhibitors, such as ivabradine and ZD7288. Moreover, certain drugs with additional HCN-blocking activities have also shown pain-attenuating actions in different pain models. There have been few studies documenting the relationship of HCN channels with other mediators of pain. Nevertheless, it may be proposed that the HCN channel activity is modulated by endogenous opioids and cyclo-oxygenase-2, whereas the activation of these channels may modulate the actions of substance P and the expression of spinal N-methyl-D-aspartate receptor subunit 2B to modulate pain. The present review describes the role and mechanisms of HCN ion channels in the development of neuropathic pain.
超极化激活和环核苷酸门控 (HCN) 通道在超极化时被激活，会有电流内流，这种电流被称为超极化激活电流 Ih。最初，这些通道在心脏的起搏细胞中被发现。如今，它们在神经系统的不同区域被发现，包括外周神经、背根神经节、背角和大脑的不同部位。有四种不同类型的 HCN 通道 (HCN1-HCN4)；然而，HCN1 和 HCN2 更为突出。大量研究表明，外周神经损伤会增加脊髓和大脑神经元中 Ih 电流的幅度。此外，在神经损伤的实验模型中，外周轴突和脊髓及大脑区域中 HCN1 和 HCN2 蛋白通道的表达增加。研究还记录了选择性 HCN 抑制剂（如伊伐布雷定和 ZD7288）的止痛作用。此外，某些具有额外 HCN 阻断活性的药物在不同的疼痛模型中也表现出止痛作用。关于 HCN 通道与其他疼痛介质的关系的研究较少。然而，可以提出的是，HCN 通道活性受内源性阿片类物质和环氧化酶-2 调节，而这些通道的激活可能调节 P 物质的作用和脊髓 N-甲基-D-天冬氨酸受体亚单位 2B 的表达，以调节疼痛。本综述描述了 HCN 离子通道在神经性疼痛发展中的作用和机制。
