内侧前额叶皮层GABA能神经元mGluR5调节慢性神经病理性痛及伴发情感障碍的机制研究

全球约有20%的人被慢性痛困扰，其中焦虑症和抑郁症等情感障碍是慢性痛患者的常见并发症。令人遗憾的是，目前对参与慢性痛导致的负性情绪的中枢神经机制了解甚少。根据本课题组前期工作基础以及既往文献，提出如下假说：慢性痛状态下，内侧前额叶皮层（mPFC）内 GABA能神经元输入环路网络发生特征性的变化，导致mPFC内GABA能神经元代谢型谷氨酸受体-5型（mGluR5）表达升高和神经元可塑性改变，促进负性情绪的发生。精准下调特定类型的GABA能神经元的mGluR5可以有效缓解慢性痛及相关的情感障碍。本研究将利用选择性坐骨神经损伤小鼠为慢性神经病理性痛模型，核心运用荧光显微光学切片断层成像技术（fMOST)，并综合运用流式细胞分选、单细胞PCR、高尔基染色、免疫电镜、化学遗传学、行为学等多种研究方法，深入探讨mPFC内GABA能神经元的mgluR5在慢性痛及伴发焦虑样和抑郁样行为中的作用机制。

About 20% of people in the world are troubled by chronic pain. Mood disorders such as anxiety and depression are common complications of chronic pain patients. Regrettably, the central nervous system involved in negative emotions caused by chronic pain is currently poorly understood. Based on the foundation of the previous work of our group and previous literature, the following hypothesis is proposed: in the state of chronic pain, the GABAergic neuron input loop network in the medial prefrontal cortex (mPFC) undergoes characteristic changes, resulting in an increase in the expression of metabotropic glutamate receptor-5 (mGluR5) on GABAergic neurons in mPFC and changes in neuronal plasticity, which in turn promotes the occurrence of negative emotions. Precisely down-regulating mGluR5 of specific types of GABAergic neurons can effectively alleviate chronic pain and related emotional disorders.This study will use selective sciatic nerve injury mice as a chronic neuropathic pain model. Fluorescence microscopy optical section tomography (fMOST), flow cytometry, single-cell PCR, Golgi staining, immunoelectron microscopy, chemogenetics and behavioral studies will be used to deeply explored the mechanism of mgluR5 of GABAergic neurons in mPFC in chronic pain and associated anxiety-like and depression-like behaviors.