慢性神经病理性疼痛是一种严重的健康问题，既是临床治疗的难点，也是疼痛研究的热点。外周神经损伤后可以激活脊髓小胶质细胞和星型胶质细胞，活化的胶质细胞释放的多种炎性趋化因子、细胞因子可以增强脊髓中间神经元的兴奋性,在神经病理性疼痛的产生和维持中发挥重要作用。本课题将对星型胶质细胞分泌的细胞外基质蛋白Hevin在神经病理性疼痛中的作用和机制开展研究。通过Hevin KO小鼠的行为学和电生理学分析，Hevin蛋白和抗体的体内外实验和以及病毒感染脊髓星型胶质细胞等方法，研究1）Hevin蛋白在神经损伤引发的急性痛转变为慢性痛的过程中起什么作用？2）Hevin增强脊髓感觉神经元兴奋性的机制是什么？3）Hevin对小胶质细胞活化的影响和机制？4）Hevin 抗体是否可以用来治疗神经病理性疼痛？该研究不仅有助于揭示星型胶质细胞在维持神经病理性疼痛中的作用，还将为治疗神经病理性疼痛提供新的思路和手段。

Chronic neuropathic pain is a serious health problem and especially difficult to treat. It is generally believed that neuropathic pain is an expression of neural plasticity in primary sensory neurons (peripheral sensitization) and CNS (e.g., spinal cord dorsal horn) neurons (central sensitization). Recent progress in pain research field has also pointed to a central role for spinal cord microglia and astrocytes in neuropathic pain. Peripheral nerve injury induces robust spinal glial cells activation. Activated glial cells produce the proinflammatory cytokines and chemokines to facilitate spinal cord synaptic transmission and promote neuropathic pain. During development astrocytes promote synapse formation and regulate synaptic connectivity in the CNS through secreted signals, such as thrombospondin-4 (TSP4) and Hevin. After nerve injury TSP4 is mainly up-regulated in spinal astrocytes and contributes to the development of neuropathic pain. On the other hand, the role of astrocyte-secreted synaptogenic protein Hevin in chronic pain is unknown. In this study, we will test the hypothesis that spinal cord astrocytic Hevin contributes to the development and maintenance of neuropathic pain caused by peripheral nerve injury. Combined with the methods of electrophsciology, virus microinjection, immunohistrochemistry, pharmacology and behaviorology in wild-type and Hevin KO mice, we will investigate (1) the role of astrocytic Hevin in the transition from acute to chronic neuropathic pain,(2) the mechanism of hevin for enhancing the excitability of spinal cord sensory neurons,(3) the role of Hevin in microglial activation, (4) whether hevin–neutralizing antibody can reduce neuropathic pain? These proposed studies may not only reveal the role of astrocytes in neuropathic pain, but also provides new ideas and methods for the treatment of neuropathic pain.