Axonal accumulation of hyperpolarization-activated cyclic nucleotide-gated cation channels contributes to mechanical allodynia after peripheral nerve injury in rat
Axonal accumulation of hyperpolarization-activated cyclic nucleotide-gated cation channels contributes to mechanical allodynia after peripheral nerve injury in rat
复制标题
超极化激活的环核苷酸门控阳离子通道的轴突积累导致大鼠周围神经损伤后机械性异常性疼痛
DOI：
10.1016/j.pain.2007.10.011
复制
发表时间：
2008-07-31
期刊：
影响因子：
7.4
通讯作者：
Wan, You
中科院分区：
文献类型：
--
作者：
Jiang, Yu-Qiu;Xing, Guo-Gang;Wan, You
外周神经损伤引起神经病理性疼痛，包括由于中枢和外周敏化引起的机械异常性疼痛和热痛觉过敏。来自背根神经节（DRG）神经元和损伤部位的自发异位放电是启动这种敏化的关键因素。许多研究主要集中在DRG神经元;然而，受损的轴突本身可能发挥同样重要的作用。以往对脊神经结扎（SNL）大鼠神经病理性疼痛的研究表明，DRG神经元胞体中超极化激活的环核苷酸门控阳离子（HCN）通道在神经病理性疼痛的发生发展中起重要作用。在这里，我们调查轴突HCN通道在神经病理性疼痛大鼠的作用。使用慢性压迫性损伤（CCI）模型，我们发现大量的HCN通道蛋白在损伤部位的轴突积聚，伴随着DRG神经元体的轻微减少。这些积聚通道的功能通过局部应用特定的HCN阻滞剂ZD 7288来验证，该阻滞剂可显着抑制受损神经纤维的异位放电，而对冲动传导没有影响。此外，ZD 7288可显著缓解机械性异常性疼痛，但不能缓解热痛觉过敏。这些结果表明，轴突HCN通道的积累起着重要的作用，异位放电损伤的脊神经，并有助于机械异常性疼痛的发展，在神经病理性疼痛大鼠。(C)2007年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
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. (C) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.