Electroacupuncture inhibits excessive interferon-γ evoked up-regulation of P2X4 receptor in spinal microglia in a CCI rat model for neuropathic pain
Electroacupuncture inhibits excessive interferon-γ evoked up-regulation of P2X4 receptor in spinal microglia in a CCI rat model for neuropathic pain
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DOI：
10.1093/bja/aeu199
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发表时间：
2015-01-01
影响因子：
9.8
通讯作者：
Wang, X. -R.
中科院分区：
文献类型：
--
作者：
Chen, X. -M.;Xu, J.;Wang, X. -R.
虽然电针对神经病理性疼痛有明显的缓解作用，但其机制尚不清楚。以往的研究报道了EA对大鼠的免疫调节作用。由于干扰素-γ的过度释放在神经损伤后，IFN-γ将静止的脊髓小胶质细胞转化为具有更多神经性疼痛的活化状态，与嘌呤能受体P2 X4表达相关，电针可能通过抑制IFN-γ的释放和随后P2 X4 R（+）小胶质细胞的产生来介导其镇痛作用。采用γ-椎管内注射和von Frey试验评价电针对痛阈的影响。脊髓IFN-γ和P2 X4 R表达水平通过免疫组织化学、实时PCR、酶免疫分析和/或蛋白质印迹法测定。用体外原代培养的小胶质细胞检测P2 X4 R（+）细胞的IFN-γ激活。在CCI大鼠中，相对于对照，EA治疗显著增加缩足阈值。IFN-γ促进P2 X4 R（+）小胶质细胞在体外和体内的活化。电针还下调CCI后脊髓中P2 X4 R和IFN-γ的表达。电针可通过下调脊髓内IFN-γ的过度表达，进而降低P2 X4 R的表达，从而改善周围神经损伤后的触觉异常性疼痛。
Although electroacupuncture (EA) is effective in the relief of neuropathic pain, the underlying mechanisms remain unclear. Previous studies have reported immunomodulatory effects of EA in rats. Since excessive release of interferon-gamma (IFN-gamma) after nerve injury transforms quiescent spinal microglia into an activated state with more neuropathic pain, associated with purinergic receptor P2X4 expression, it is possible that EA may mediate its analgesic effect by attenuating IFN-gamma release and subsequent generation of P2X4R(+) microglia.Male rats underwent chronic constriction injury (CCI) or IFN-gamma intrathecal injection and von Frey tests were performed to evaluate the effect of EA on pain thresholds. Spinal IFN-gamma and P2X4R expression levels were measured by immunohistochemistry, real-time PCR, enzyme immunoassay, and/or western blots. In vitro primary cultures of microglia were used to examine IFN-gamma activation of P2X4R(+) cells.In CCI rats, EA treatment significantly increased paw withdrawal threshold relative to control. IFN-gamma facilitated P2X4R(+) microglia activation both in vitro and in vivo. EA also down-regulated both P2X4R and IFN-gamma expression in the spinal cord after CCI. However, EA did not exert the same analgesic effect after intrathecal IFN-gamma injection.EA ameliorated tactile allodynia after peripheral nerve injury by down-regulating excessive expression of IFN-gamma in the spinal cord and subsequently reducing expression of P2X4R.