Jiang Yu-Qiu, Xing Guo-Gang, Wang Sheng-Lan, Tu Hui-Yin, Chi Ye-Nan, Li Jie, Liu Feng-Yu, Han Ji-Sheng, Wan You
Neuroscience Research Institute, Peking University, Beijing 100083, China Department of Neurobiology, Peking University, Beijing 100083, China Key Laboratory for Neuroscience, Peking University, Beijing 100083, China Department of Pathology, Peking University, Beijing 100083, China.
Pain. 2008 Jul 31;137(3):495-506. doi: 10.1016/j.pain.2007.10.011. Epub 2008 Jan 7.
Peripheral nerve injury causes neuropathic pain including mechanical allodynia and thermal hyperalgesia due to central and peripheral sensitization. Spontaneous ectopic discharges derived from dorsal root ganglion (DRG) neurons and from the sites of injury are a key factor in the initiation of this sensitization. Numerous studies have focused primarily on DRG neurons; however, the injured axons themselves likely play an equally important role. Previous studies of neuropathic pain rats with spinal nerve ligation (SNL) showed that the hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel in DRG neuronal bodies is important for the development of neuropathic pain. Here, we investigate the role of the axonal HCN channel in neuropathic pain rats. Using the chronic constriction injury (CCI) model, we found abundant axonal accumulation of HCN channel protein at the injured sites accompanied by a slight decrease in DRG neuronal bodies. The function of these accumulated channels was verified by local application of ZD7288, a specific HCN blocker, which significantly suppressed the ectopic discharges from injured nerve fibers with no effect on impulse conduction. Moreover, mechanical allodynia, but not thermal hyperalgesia, was relieved significantly by ZD7288. These results suggest that axonal HCN channel accumulation plays an important role in ectopic discharges from injured spinal nerves and contributes to the development of mechanical allodynia in neuropathic pain rats.
周围神经损伤会引发神经性疼痛，包括由于中枢和外周敏化导致的机械性异常性疼痛和热痛觉过敏。源自背根神经节（DRG）神经元以及损伤部位的自发性异位放电是这种敏化起始的关键因素。众多研究主要聚焦于DRG神经元；然而，受损轴突本身可能发挥着同样重要的作用。先前对脊髓神经结扎（SNL）所致神经性疼痛大鼠的研究表明，DRG神经元胞体中的超极化激活环核苷酸门控阳离子（HCN）通道对神经性疼痛的发展至关重要。在此，我们研究轴突HCN通道在神经性疼痛大鼠中的作用。利用慢性压迫损伤（CCI）模型，我们发现在损伤部位HCN通道蛋白大量积聚于轴突，同时DRG神经元胞体略有减少。通过局部应用特异性HCN阻滞剂ZD7288证实了这些积聚通道的功能，ZD7288可显著抑制受损神经纤维的异位放电，而对冲动传导无影响。此外，ZD7288可显著缓解机械性异常性疼痛，但对热痛觉过敏无作用。这些结果表明，轴突HCN通道的积聚在受损脊髓神经的异位放电中起重要作用，并促成了神经性疼痛大鼠机械性异常性疼痛的发展。
