α2A受体介导的脊髓背角神经元IFN-γ表达调控在电针治疗关节炎性痛中的作用研究

Arthritic pain is a pathological pain dampening human health and quality life. Electroacupuncture (EA) could effectively relive arthritic pain. However, the associated mechanism is still lack. My preliminary study has found EA could downregulate neuronal IFN-γ expression in the spinal dorsal horn, which contributed to the development of arthritic pain. ①The IFN-γ expression was regulated by α2A-adrenoceptor, which expressed on neuron in the spinal dorsal horn; ②α2A receptor could be activated by EA. In light of the above, we hypothesize that EA could decrease IFN-γ expression to inhibit spinal long-term potentiation (LTP) by activating α2A receptor in the spinal cord, which results in arthritic pain attenuation. Next, we will observe the impact of EA on IFN-γ expression, spinal LTP, and pain behavior in monoarthritic rat model. Furthermore, a key role of spinal IFN-γ modulated by α2A receptor in EA-induced treatment of arthritic pain will determined by drug application and delivery of adeno-associated virus to intervene IFN-γ expression and α2A receptor function. Elucidation of mechanisms of EA-induced analgesia on arthritic pain from a view of neuron-mediated neuroinflammation could provide a scientific basis for clinical application of EA in arthritic pain.

关节炎性痛是一种严重危害患者身心健康的病理性疼痛，中医针刺可有效缓解关节炎性痛，但机制尚不明确。本人前期研究发现，脊髓背角神经元释放的γ干扰素（IFN-γ）是导致关节炎性痛的关键原因，而电针可以下调脊髓IFN-γ的表达。鉴于①脊髓背角神经元表达α2A受体，IFN-γ的表达受α2A肾上腺素受体的调控；②电针可激活脊髓α2A受体；我们提出假说：电针通过激活脊髓背角神经元α2A受体，抑制神经元释放IFN-γ，抑制脊髓长时程增强（LTP），缓解关节炎性痛。本项目拟采用单关节炎大鼠，观察电针对IFN-γ释放、脊髓LTP和痛觉敏化的影响，并通过病毒转导、药理学手段干预IFN-γ、α2A受体表达，明确α2A受体介导的脊髓背角神经元IFN-γ表达调控在电针治疗关节炎性痛中的关键作用，旨在从调控神经元介导的脊髓神经炎症角度阐释电针作用机理，为促进和优化电针在关节炎性痛中的临床应用提供理论依据。

关节炎性痛是一种严重危害患者身心健康的病理性疼痛，中医针刺可有效缓解关节炎性痛，但机制尚不明确。本项目利用单关节炎（MA）大鼠模型，运用行为学检测、qRT-PCR、免疫荧光组织化学方法、蛋白质免疫印迹等实验方法进行了研究。结果显示，电针能够缓解关节炎性痛；电针的镇痛作用与其下调脊髓背角神经元IFN-γ表达相关；且α2A受体参与调控MA大鼠脊髓IFN-γ表达。此外运用膜片钳记录，结果发现α2A受体激动剂—右美托咪定可通过兴奋神经元α2A受体，抑制酸敏感性离子通道介导的内向电流，从而发挥镇痛作用。鉴于既往研究发现电针的镇痛作用与其抑制小胶质细胞活化相关，本项目中进一步探讨了小胶质细胞介导的神经炎症在电针治疗单关节炎大鼠疼痛中的作用。研究结果表明，电针可通过抑制P2Y12R介导的小胶质细胞激活，抑制脊髓神经炎症，从而产生镇痛作用。本研究为促进和优化电针在关节炎疼痛中的临床应用提供了理论依据。