基于皮层扩散性抑制探讨针刺预防性治疗偏头痛的机制

Migraine has a tremendous impact on the quality of life. Preventive treatment of migraine by acupuncture is effective, but the mechanism is not clear. Cortical spreading depression (CSD) is the pathological basis of migraine with aura and migraine attacks, cortical excitability, which is caused by abnormalities of ion channels in the cerebral cortex neurons, will reduce the CSD threshold. According to this we put forward a working hypothesis: acupuncture preconditioning can change the susceptibility of neurons to CSD by the intervention of sodium and calcium channels in order to inhibit the production of the CSD, thus prevent the occurrence of migraine and achieve the purpose of prevention. In this experiment, we use the CSD rat model for the study, starting from the ion channels that can lower CSD threshold, using whole-cell patch-clamp technique, Western-Blot technology to observe the inhibition of acupuncture pretreatment on the CSD and sodium, calcium channel in the cortical neurons neuronal. We explore the mechanism of inhibition of ion channel that can lower CSD threshold from the two levels of cells, proteins. Different from the previous research ideas of acute phase analgesic mechanism and neurotransmitter detection indicators, we provide new scientific evidence for the prophylactic treatment of acupuncture.

偏头痛对生活质量影响巨大，针刺预防性治疗偏头痛疗效确切，但治疗机制尚不明确，皮层扩散性抑制（CSD）是偏头痛先兆及头痛发作的病理基础，大脑皮层神经元离子通道的异常导致的皮层兴奋性会降低CSD发生的阈值。据此提出工作假说：针刺预处理可以通过干预钠通道和钙通道改变神经元对CSD的易感性,抑制CSD的产生,从而防止偏头痛的发生,达到预防目的。本实验以CSD模型大鼠为研究对象，从降低CSD发生阈值的离子通道变化为切入点，采用全细胞膜片钳技术、Western-Blot等技术，观察针刺预处理对CSD的抑制作用及皮层神经元钠、钙离子通道的影响，从细胞、蛋白两个水平上探讨针刺预处理抑制CSD发生的离子通道作用机制。有别于以往的多从急性期镇痛机制及神经递质检测指标入手，为针刺的预防性治疗提供科学依据。

偏头痛对生活质量影响巨大，针刺预防性治疗偏头痛疗效确切，但治疗机制尚不明确，皮层扩散性抑制（CSD）是偏头痛先兆及头痛发作的病理基础，大脑皮层神经元离子通道的异常导致的皮层兴奋性会降低CSD发生的阈值。据此提出工作假说：针刺预处理可以通过干预钠通道和钙通道改变神经元对CSD的易感性,抑制CSD的产生,从而防止偏头痛的发生,达到预防目的。本实验以CSD模型大鼠为研究对象，从降低CSD发生阈值的离子通道变化为切入点，采用全细胞膜片钳技术、Western-Blot等技术，观察针刺预处理对CSD的抑制作用及皮层神经元钠、钙离子通道的影响，从细胞、蛋白两个水平上探讨针刺预处理抑制CSD发生的离子通道作用机制。有别于以往的多从急性期镇痛机制及神经递质检测指标入手，为针刺的预防性治疗提供科学依据。通过本次研究，我们成功获得适合膜片钳记录的CSD大鼠皮层椎体神经元，观测到CSD后皮层椎体神经元钙、钠离子通道的特征性改变。发现针刺和药物的预处理均可以干预CSD，降低CSD模型大鼠的CGRP含量，抑制钙通道电流幅度和电流密度峰值；针刺预处理可以升高钠通道激活的电压阈值，药物预处理可以降低钠通道电流幅度和电流密度峰值。针刺可能是通过改变大鼠皮层锥体神经元钠通道和钙通道的开放特性，进而影响CSD 的发作程度，间接抑制了三叉神经血管系统的激活，这可能是针刺预防性治疗偏头痛的作用机制之一。