阿片肽与脊髓背角小胶质细胞上的阿片经典受体和toll样受体(TLR)结合分别诱导"镇痛"与"痛敏"两种相反的中枢免疫信号，二者具有竞争抑制作用。申请者以往的实验结果表明，电针产生累积镇痛效应时，脊髓背角TLR4的表达明显下降。那么，电针是否通过激活小胶质细胞上的经典阿片受体途径而抑制了TLR的表达？这可能与针刺镇痛效应直接相关。本研究通过观察CCI大鼠脊髓背角小胶质细胞上这两种阿片受体诱导的免疫信号在电针干预不同时期的动态变化来分析阿片经典受体对TLR的抑制作用及相关机制，并特异性阻断阿片经典受体下游相关的免疫信号通路，分析这些免疫信号在电针镇痛中的贡献度。通过在小胶质细胞上分析针刺调动内源性镇痛的机制，把针刺镇痛研究推进到细胞免疫的更高层次，为证明针刺如何充分调动机体的内源性镇痛系统，进一步提高临床疗效奠定理论基础。

The central immune signalings in microglia induced via opioid action amplification of classic opioid receptors and via activation of toll-like receptor (TLR)-dependent signaling suggest a competition between the "analgesia" and the "hyperalgesia". Our previous research displayed a cumulative analgesic effect of repeated electroacupuncture (EA) stimulation of Zusanli (ST36)-Yanglingquan (GB34), accompaning with a decreased TLR4 expression in the spinal dorsal horn. Whether EA intervention induced an inhibition of the TLR-dependent immune signaling by activation of the classic opioid receptors results in pain relief? It remains unclear up to now. The present study is designed to examine the dynamic changes of endogenous opioid peptides, TLR4 and classic opioid receptors (μ, κ and δ) of the microgliacytes in the lumbar spinal dorsal horns after EA treatment in chronic neuropathic pain rats by using real-time PCR, western blot, fluorescent immunohistochemistry, confocol laser scanning microscope, enzyme linked immunosorbent assay, flow cytometry, intrathecal injection of specific antagonists of some downstream signaling pathways, etc., so as to determine their relationship during pain development and analgesic process, and to validate the contribution of these two types opioid receptors induced immune signalings to acupuncture analgesia. This study will provide scientific evidence for reveling the mechanism of acupuncture intervention induced reduction of chronic neuropathic pain by regulating spinal immunocellular signaling.