中文摘要
以往研究显示针刺外周穴位治疗神经病理性痛(NP)与调控脊髓水平的伤害感受性通路有关。我们前期研究发现电针头部百会穴也可缓解神经损伤后的痛觉过敏,但机制不明。中脑触液核ATP-P2X4Rs信号通路在NP的发生和发展中起关键作用,并受ATP水解酶5’-外核苷酸酶(NT5E)调控。鉴于电针可通过激活肾上腺素能神经通路,增加NT5E的活性,我们提出假说:触液核ATP-P2X4Rs信号通路是电针百会穴治疗NP的关键靶点,即电针通过增强脑内NT5E活性,降低ATP水平,减少P2X4受体激活,缓解NP。本项目拟采用坐骨神经结扎大鼠模型,观察电针对触液核ATP-P2X4Rs、NT5E和疼痛的影响,通过激动/拮抗剂、基因过表达或敲减等干预手段,明确触液核ATP-P2X4Rs信号通路在电针百会穴治疗NP中的作用,旨在从脊髓上中枢水平揭示电针百会穴治疗NP的机制,为拓展针刺百会穴的临床应用范围提供理论依据。
英文摘要
Electroacupuncture at peripheral acupoints could be used for the treatment of neuropathic pain, and the involved mechanism was associated with the spinal nociceptive pathway. Our preliminary results found that electroacupuncture at Baihui attenuated the hyperalgesia induced by nerve damage, while the mechanisms remains elusive. Previous reports indicated that ATP-P2X4Rs pathway in cerebrospinal fluid-contacting nucleus (CSF-CN) play critical role in the pathogenesis of neuropathic pain, and ecto-5’-nucleotidase (NT5E) which hydrolyze ATP to adenosine are involved in the regulation of these processes. In addition, electroacupuncture could increase the activity of NT5E through the activation of the adrenergic nerve system. Based on these, we render such hypotheses: electroacupuncture at Baihui could increase the NT5E activity in brain, decrease ATP levels, resulting in the deactivation of P2X4Rs in CSF-CN ultimately lead to the attenuation of neuropathic pain. In these research, the chronic constriction injury rat model will be used to observe the effect of electroacupuncture at Baihui on ATP-P2X4Rs in CSF-CN, NT5E levels, and pain. The agonist or antagonist, and overexpression or knockdown of ATP-P2X4Rs will be used to elucidate the mechanisms of the treatment effect produced by electroacupuncture at Baihui. These work will reveal the roles of ATP-P2X4Rs in neuropathic pain with electroacupuncture at Baihui and provide the theory basis for its wide clinical use.
