基于TCC核团miRNA介导的神经元-星形胶质细胞互作途径探讨针刺干预慢性偏头痛中枢敏化的机制研究

慢性偏头痛核心病机是中枢敏化。三叉神经血管系统TCC核团神经元过度激活可引起中枢敏化，外在表现为皮肤异常疼痛。申请人前期研究证实针刺可抑制慢性偏头痛模型TCC核团神经元异常放电而缓解皮肤异常疼痛。最新研究发现miRNA从表观遗传学水平介导的神经元-星形胶质细胞互作也参与中枢敏化形成。据此，本研究提出“针刺通过表观遗传学分子miRNA，调控神经元-星形胶质细胞CXCL13/CXCR5复合体形成，抑制CXCR5/ERK依赖的中枢敏化相关通路，干预痛觉信息传递”的假说，选用反复硬脑膜注射炎症汤的慢性偏头痛模型，以TCC核团miRNA介导的神经元-星形胶质细胞互作途径为核心，应用分子探针介导的Micro-PET、在体电生理、荧光原位杂交等技术，探索针刺干预慢性偏头痛中枢敏化的潜在靶点及机制。

The main pathogenesis of chronic migraine is central sensitization. Excessive activation of neurons in the TCC nucleus of the trigeminal vascular system can cause central sensitization, and the external manifestation is cutaneous allodynia. Our previous study confirmed that acupuncture can inhibit abnormal discharge of neurons in TCC nuclei and alleviate cutaneous allodynia in a chronic migraine model. The latest research found that the neuron-astrocyte interaction mediated by miRNA from the epigenetic level is also involved in the formation of central sensitization. Accordingly, our study proposes the hypothesis that "acupuncture regulates the formation of CXCL13/CXCR5 complex of neuron-astrocyte by epigenetic molecular miRNA, inhibits CXCR5/ERK-dependent central sensitization-related pathways, and intervenes with the transmission of pain information". In this study, based on the theory that miRNA-mediated neuron-astrocyte interaction pathway in the TCC nuclear, we will explore the potential targets and mechanisms underlying acupuncture for central sensitization in a chronic migraine with repeated dural injection of inflammation soup, using molecular probe-mediated Micro-PET, electrophysiology and fluorescence in situ hybridization.