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神经病理性疼痛增强HCN2通道在大鼠触液核的表达

吴桐, 曹静, 张励才^*

徐州医学院江苏省麻醉学重点实验室,徐州 221004

摘要

本文旨在研究超极化激活环核苷酸门控通道亚型2 (hyperpolarization-activated cyclic nucleotide-gated channels subtype 2, HCN2)在触液核的分布及其在神经病理性疼痛条件下的表达变化，以期为揭示触液核的生物学功能及神经病理性疼痛的调控机制提供实验依据。以Sprague-Dawley (SD)大鼠为实验动物，用坐骨神经慢性压迫损伤(chronic constriction injury, CCI)法制作神经病理性疼痛模型，用侧脑室注射辣根过氧化物酶标记的霍乱毒素B亚单位复合物(CB-HRP)特异性标记触液核神经元，用热缩足潜伏期及机械缩足阈值作为定量指标研究痛行为，用免疫荧光法及Western blot检测触液核HCN2通道蛋白及c-Fos蛋白的表达量。结果显示，与正常大鼠相比，接受侧脑室CB-HRP注射的大鼠痛阈及触液核HCN2、c-Fos表达均无明显变化；而CCI术后第7、14天，神经病理性疼痛模型大鼠痛阈显著下降，且触液核神经元的HCN2通道蛋白及c-Fos蛋白的表达显著增加。使用HCN2阻断剂ZD7288后，CCI致痛大鼠痛阈显著提高，触液核神经元HCN2通道蛋白及c-Fos蛋白的表达较相应时间点模型组显著降低，以术后第7、14天为明显。以上结果提示，触液核可能参与了神经病理性疼痛的调制，且通过HCN2通道发挥重要作用。

关键词： 触液核; 超极化激活环核苷酸门控通道亚型2; 离子通道; c-Fos; ZD7288; 神经病理性疼痛

[Neuropathic pain enhances expression of HCN2 channel in rat CSF-contacting nucleus.] [Article in Chinese]

WU Tong, CAO Jing, ZHANG Li-Cai^*

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China

Abstract

The purpose of this research is to explore the distribution and expression of hyperpolarization-activated cyclic nucleotide-gated channels subtype 2 (HCN2) in cerebrospinal fluid (CSF)-contacting nucleus in neuropathic pain, and provide experimental evidence to reveal the biological function and regulation mechanisms of CSF-contacting nucleus in neuropathic pain. Neuropathic pain model was produced by chronic constriction injury (CCI) in Sprague-Dawley (SD) rats. Intracerebroventricular injection of cholera toxin subunit B (CTb) labeled with horseradish peroxidase (CB-HRP) was used to specifically mark distal CSF-contacting nucleus. The thermal withdrawal latency and mechanical withdrawal threshold of rats were recorded to detect the change of pain threshold. The expressions HCN2 channel and c-Fos proteins in CSF-contacting nucleus were detected by immunofluorescence and Western blot. The results showed that, compared with the control group, CTb-treated rats did not show any differences in the expressions of HCN2 channel and c-Fos proteins in CSF-contacting nucleus, as well as pain threshold. At 7, 14 d after CCI operation, the model rats showed not only significantly increased expressions of HCN2 channel and c-Fos in CSF-contacting nucleus, but also decreased pain threshold. ZD7288, a HCN2 channel blocker, could reverse the above changes in neuropathic pain model rats. These results suggest that the CSF-contacting nucleus may be involved in the process of neuropathic pain via the HCN2 channel.

Key words: CSF-contacting nucleus; hyperpolarization-activated cyclic nucleotide-gated channels subtype 2; ion channel; c-Fos; ZD7288; neuropathic pain

收稿日期：2013-12-17　　录用日期：2014-02-10

通讯作者：张励才　　E-mail: lczhang@xzmc.edu.cn

引用本文：

吴桐, 曹静, 张励才. 神经病理性疼痛增强HCN2通道在大鼠触液核的表达[J]. 生理学报 2014; 66 (3): 323-331.

WU Tong, CAO Jing, ZHANG Li-Cai. [Neuropathic pain enhances expression of HCN2 channel in rat CSF-contacting nucleus.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (3): 323-331 (in Chinese with English abstract).