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外周NFκB参与强直刺激坐骨神经引起的神经病理性痛

王喆辰, 吕宁, 张玉秋^*

复旦大学神经生物学研究所，上海 200032

摘要

强直电刺激大鼠坐骨神经(tetanic stimulation of the sciatic nerve, TSS)能够引起脊髓背角C纤维和A纤维介导的场电位的长时程增强(long-term potentiation, LTP)。以往对其机制的研究多集中在脊髓水平，而对外周的变化了解甚少。核因子kappa B (nuclear factor kappa B, NFκB)是一种重要的转录因子，脊髓NFκB的激活与多种促炎性细胞因子的合成与释放以及脊髓胶质细胞的激活密切相关，提示其可能参与神经病理性痛的的中枢敏化。为了明确在初级感觉神经元中NFκB是否参与外周敏化，本研究通过痛行为学测试、免疫荧光组织化学、免疫印迹等方法，观察到TSS能够引起大鼠双侧后肢的持续性触诱发痛和双侧背根神经节(dorsal root ganglia, DRG)中磷酸化的NFκB (激活形式的NFκB)表达上调；这些激活的NFκB主要表达在神经元、施旺细胞和卫星胶质细胞的细胞核内；给予选择性NFκB抑制剂PDTC能够明显缓解TSS引起的触诱发痛。这些结果提示外周NFκB也参与TSS诱导的神经病理性痛，并首次为单侧坐骨神经损伤引起双侧“镜像痛”的外周机制提供了新的证据。

关键词： NFκB; 强直刺激坐骨神经; 触诱发痛; 神经病理性痛; 镜像痛

分类号：Q426

[Involvement of peripheral NFκB in tetanic sciatic stimulation-induced neuropathic pain.] [Article in Chinese]

WANG Zhe-Chen, LU Ning, ZHANG Yu-Qiu^*

Institute of Neurobiology, Fudan University, Shanghai 200032, China

Abstract

Tetanic stimulation of the sciatic nerve (TSS) induces long-term potentiation (LTP) of both C- and A-fiber-evoked field potentials in the spinal dorsal horn and long-lasting mechanical allodynia in rats. Though central mechanisms underlying those phenomena have been well studied, peripheral mechanisms still remain poorly known. Nuclear factor kappa B (NFκB) is an important transcription factor. In the spinal cord, NFκB plays a key role in regulating the expression of numerous pro-inflammation factors and contributes to glial activation in central nervous system, suggesting the involvement of spinal NFκB in central sensitization. To address whether NFκB in the dorsal root ganglion (DRG) participates in peripheral sensitization, we examined NFκB expression in the DRG and the effect of inhibiting NFκB activation on neuropathic pain using behavior test, Western blot analysis and immunohistochemical approaches. The results showed that TSS induced long-lasting mechanical allodynia in bilateral hind paws and increased phospho-NFκB expression in the bilateral DRG. The activated NFκB mainly expressed in nuclei not only of neurons, but also of Schwann cells and satellite glial cells. Moreover, NFκB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly alleviated TSS-induced allodynia. Our results suggest that peripheral NFκB may be involved in TSS-induced neuropathic pain, and provide new evidence for the peripheral mechanism of 'mirror pain'.

Key words: NFκB; Tetanic stimulation of sciatic nerve (TSS); allodynia; neuropathic pain; mirror pain

收稿日期：2013-08-30　　录用日期：2013-09-10

通讯作者：张玉秋　　E-mail: yuqiuzhang@fudan.edu.cn

引用本文：

王喆辰, 吕宁, 张玉秋. 外周NFκB参与强直刺激坐骨神经引起的神经病理性痛[J]. 生理学报 2013; 65 (5): 489-496.

WANG Zhe-Chen, LU Ning, ZHANG Yu-Qiu. [Involvement of peripheral NFκB in tetanic sciatic stimulation-induced neuropathic pain.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (5): 489-496 (in Chinese with English abstract).