背根神经节中的成纤维细胞在神经病理性痛调控中的作用及机制研究

背根神经节(DRG)中感觉神经元和卫星胶质细胞在神经病理性痛发病或调控机制的研究中都受到密切关注。成纤维细胞也是DRG的固有细胞之一，但其在正常和病理性痛调控中的作用至今都缺乏研究。DRG中卫星胶质细胞通过相互间的紧密连接而包裹着感觉神经元的胞体。但我们最近发现成纤维细胞定位在卫星胶质细胞外且相互连接分隔了相邻的神经元，发挥了“物理阻隔”作用。相比而言，成纤维细胞在大脑或脊髓中没有这种分布和功能。神经病理性痛情况下成纤维细胞的“物理阻隔”作用受损，而导致相邻的神经元形成可相互影响的“神经元群”。而神经元群的产生可能是病理性的机械性痛觉异常的重要发病原因。因此，本项目将从新的角度研究背根节中成纤维细胞在神经病理性痛调控中的作用和分子机制，以及成纤维细胞与卫星胶质细胞、感觉神经元的交互作用。本项目将拓展我们对神经病理性痛发病机制的认知，也将为镇痛药物研发提供新的方向。

Sensory neurons and satellite glial cells in the dorsal root ganglia (DRG) have been paid close attention in the study of the pathogenesis and regulatory mechanisms of neuropathic pain. Fibroblasts are also the intrinsic cells within DRG. However, their functions under normal and pathological pain condition have been poorly studied. In DRG, each soma of sensory neuron is enwrapped by a layer of satellite glial cells connecting tightly by gap junctions. But we discovered that fibroblasts were located outside the satellite glial cells, and were connected to each other to separate adjacent sensory neurons by playing a "physical blocking" role. Comparatively, fibroblasts in the brain or spinal cord did not show the distinct distribution, or have the specific function. Under neuropathic pain condition, the "physical blocking" of fibroblasts was impaired, resulting in the formation of the neuron group by adjacent sensory neurons that could interacted with each other. The abnormal neuron group could be an important cause of pathologic mechanical allodynia. Therefore, we would study the role and molecular mechanism of fibroblasts underlying the regulation of neuropathic pain in this project from. We would explore the interaction between fibroblasts, satellite glial cells and sensory neurons under pathologic pain. This project will expand our understanding of the pathogenesis of neuropathic pain, and provide a new perspective for the development of analgesics.