电针影响前扣带皮层神经元活动缓解痛情绪的作用及机制研究

Pain is a disease, and also the common symptoms of various illnesses, that has been being particularly difficulty in cure, and brought enormous economic and emotional burden in society. Pain-related affective response, an important component of pain, heavily reduces patients' quality of life, but research of affective pain is largely lagged behind that of sensory-discriminative component of pain. The mechanisms of the affective pain and the therapeutical targets are not determined. Researches show that anterior cingulate cortex (ACC) play key role in pain-related affective response. Our previous study demonstrated that electroacupuncture (EA) significantly alleviated affective pain through activating rostral (rACC) opiate system in a model of inflammatory pain. It has been found by pilot experiments that EA markedly inhibited the phosphorylation of NR1 in rACC; the NMDA receptors are co-expressed with μ receptors in rACC neurons. We hypothesis that EA can increase the release of endogenous opioid, and activate opioid receptors, which then inhibit the phosphorylation of NR1, NR2A and NR2B in rACC, thereby alleviate pain-related affective response. In this study, we will apply CFA-injected inflammatory pain model in hind paw and conditioned place avoidance (CPA) test, and use multichannel data acquisition system, Double immunofluorescence and Western-blot technologies, to explore the mechanisms that EA stimulate Huantiao (GB30) acupoint to alleviate pain-related affective response, and provide new ideas for exploring the mechanisms on affective pain and treat chronic pain.

疼痛包括痛感受和痛情绪，虽然痛情绪严重危害患者的身心健康，但对它的研究却远滞后于对痛感受的研究。本研究的目的是：用后脚掌注射CFA结合条件性位置逃避的行为测试，使用药理学、免疫组化、Western-blot和在体多通道电生理技术，揭示电针刺激环跳穴（GB30）缓解痛情绪的机制。研究表明，前扣带回皮层（ACC）NMDA受体参与疼痛情绪反应的形成。我们前期的研究提示电针可激活吻端ACC（rACC）阿片系统缓解痛情绪。预实验发现：电针可明显地抑制rACC内NMDA受体亚单位NR1的磷酸化；NMDA受体和μ受体共表达于rACC神经元。据此，我们假设：电针刺激引起rACC释放的内源性阿片肽，可激活阿片受体，通过抑制NMDA受体亚单位NR1，NR2A和NR2B的磷酸化，调节rACC神经元的放电活动，从而缓解痛情绪。本研究将揭示痛情绪的发生以及电针缓解痛情绪的机制，为抗痛治疗提供新的理论基础和新的思路。

中文摘要：疼痛包括痛感受和痛情绪，虽然痛情绪严重危害患者的身心健康，但对它的研究却远滞后于对痛感受的研究。已知电针具有镇痛功效，本研究是用后脚掌注射CFA结合条件性位置逃避的行为测试，使用药理学、免疫组化、Western-blot和在体多通道电生理技术，揭示电针刺激环跳穴（GB30）缓解痛情绪的机制。研究表明，1）给大鼠脚掌注射CFA结合环境适应诱导的条件位置逃避（CPA）反应可以较好地反映大鼠的痛情绪反应。2）在持续性伤害性信息传入的同时，前扣带回皮层（ACC）NMDA受体的NR1、NR2A和NR2B亚基的磷酸化水平都上调，参与疼痛情绪反应的形成。3）电针刺激环跳穴可激活吻端前扣带皮层（rACC）阿片系统，包括μ-、δ-和κ-阿片受体，降低NR1、NR2A和NR2B的磷酸化水平、抑制神经元的兴奋性、减轻了CPA反应。据此，我们当初申请课题时做出的假设，即电针刺激引起rACC释放的内源性阿片肽，可激活阿片受体，通过抑制NMDA受体亚单位NR1，NR2A和NR2B的磷酸化，调节rACC神经元的放电活动，从而缓解痛情绪是成立的。我们的研究基本上完成了本研究目的，为揭示痛情绪发生和电针缓解痛情绪的更深层机制打下了基础。本研究的核心数据还在处理中，尚无高水平文章发表。目前已发表国家级文章8篇，实用新型专利2项，培养硕士研究生12人（其中毕业8人、在读4人）。