基于功能磁共振成像和脑微透析的耳针治疗原发性痛经的中枢机制研究

Primary dysmenorrhea is a common disorder with a high incidence in women, which has a serious impact on the patient's quality of life. The neuroimaging studies had shown that the incidence of PDM was associated with the abnormal changes of brain function in patients，the aberrant network including default mode network, salience network, executive control network and sensorimotor networks.. Auricular acupuncture is an effective treatment for PDM, but the underlying mechanism is unknown. Auricular acupuncture studies had shown that auricular acupuncture treatment might act through the activation of the auricular-vagal-visceral reflex pathway. In addition, neuroimaging studies had also shown that ear acupuncture stimulation could activate medulla and the high-level center above, including limbic-paralimbic system, the default mode network and sensorimotor areas. Therefore, we speculate that the mechanism of auricular acupuncture in PDM might be the regulation of auricular acupuncture on the vagus nerve and the abnormally altered brain network of PDM. In this study, we propose to explore the brain network mechanism of auricular acupuncture in PDM through the use of mutimodal magnetic resonance imaging technique, functional connectivity and independent component analysis methods. Then, based on previous imaging studies, brain regions involved in analgesia were set as regions of interest (ROIs), dysmenorrhea model rats and brain microdialysis techniques were used to detect changes in neurotransmitter content of pain-related substances in the ROIs, hoping to further reveal the neuroendocrine mechanism of auricular acupuncture treatment for PDM.

原发性痛经（PDM）发病率高，给患者的生活质量带来严重影响。影像学研究表明PDM的发病与患者大脑功能异常改变相关。耳针治疗PDM疗效肯定，但机制不明。研究表明耳穴治疗可能的通过激活耳-迷走神经-内脏反射通路来起作用的，另外耳针影像学研究还显示耳穴刺激可以激活延髓及以上的高级中枢，包括边缘叶-旁边缘叶脑区，默认缺省网络和感觉运动相关脑区。因此我们推测耳针是通过调节迷走神经及痛经异常改变脑网络来起作用的。本研究借助功能磁共振成像方法，以PDM患者为研究对象，运用功能连接度及独立成分方法来探索耳针治疗PDM的脑网络机制。然后，以前期的影像研究为基础，将参与耳针镇痛的脑区设置为感兴趣区，以痛经模型大鼠为研究对象，采用脑微透析技术活体探测种子点疼痛相关神经递质含量变化，以期更深入的揭示耳针治疗PDM的神经内分泌机制。

原发性痛经（PDM）是临床最常见的妇科疾病之一，耳穴治疗PDM疗效确切但机制不明。本研究以PDM患者为研究对象，选取指南推荐耳穴为试验组，选取痛经非相关耳穴为对照组，采用耳揿针进行预防性治疗三个月经周期，随访一个月。以痛经症状回顾量表作为主要观察指标评测两组的临床疗效，并在治疗前后采集受试者静脉血及脑影像数据以探索其治疗机制。结果表明耳揿针刺激两组耳穴均能够有效缓解痛经的发病，总有效率分别为66%和70.27%，疗效相当。随访期试验组总有效率（78%）高于对照组（59.64%），提示试验组的累积效应优于对照组。两组选穴均能够有效调节患者血清致痛物质的含量，试验组对皮质醇和P物质含量的调节优于对照组。基于功能磁共振成像的研究结果显示，治疗前后对比发现耳揿针刺激主要对背外侧前额叶，内侧前额叶，前扣带、中扣带、楔前叶、中央前回、中央后回、补充运动区等脑区功能进行调节，耳揿针对额顶网络， DMN网络，执行控制网络及感觉运动网络的调节可能是不同患者存在疗效差异的关键脑网络机制，对DMN网络关键脑区进行功能链接（FC）分析发现，耳揿针治疗后左侧楔前叶与右侧眶回的FC增加；右侧楔前叶与左侧枕中回、双侧豆状核的FC增加，与左侧背外侧前额叶的FC降低；左侧后扣带与左侧背外侧前额叶的FC降低；右侧后扣带与右侧额中回、左侧楔前叶的FC增加。动物实验研究中，耳甲电刺激能够有效的增加痛经模型大鼠的扭体反应潜伏期，降低扭体反应评分，且优于模型组，但与对照组相比无明显统计学差异。耳甲电刺激能够促进痛经模型大鼠的子宫PGE2含量增加，降低PGF2α含量，与耳尖组及迷走神经阻断组相比无明显统计学差异。基于前期影像学研究结果，将扣带回作为目标脑区，采取微透析方法对扣带回内五羟色胺和去甲肾上腺素含量进行探测，揭示耳揿针镇痛的神经内分泌机制。