靶向抑制神经毒害型A1型星形胶质细胞生成，有望在保留星形胶质细胞正常生理功能的前提下，防止术后疼痛慢性化。我们前期研究发现，脊髓和背根神经节内上调的Wnt5a参与术后慢性疼痛，鞘内拮抗Wnt5a可降低活化的星形胶质细胞和Ror2；但关于星形胶质细胞活化类型、功能及调控机制尚未阐明。离体研究中发现，A1型标记物C3激活后的分解片段C3a，其受体（C3aR）在基因启动子区域可被AP-1结合，而Wnt5a/Ror2能特异性调控AP-1活化。基于此，我们提出，脊髓星形胶质细胞内Wnt5a/Ror2通过上调AP-1启动核内C3aR转录，进而促进C3表达、A1型活化，最终导致慢性疼痛。研究拟应用C3aR-/-、Ror2-/-特异性敲除小鼠，结合多项分子生物学技术，探讨脊髓A1型在术后慢性疼痛中的作用，及Wnt5a/Ror2/AP-1对A1型活化的调控，为今后靶向干预术后慢性疼痛提供新思路和理论依据。

Reactive astrocytes may play a key role in the transition from acute to chronic post-surgical pain. Targeted inhibition of A1 astrocytes activation is promised to prevent chronic pain while maintaining its normal function. Our previous study have found that, the upregulated Wnt5a in the spinal cord and dorsal root ganglion is involved in chronic post-surgical pain, and intrathecal inhibition of Wnt5a could downregulate the activated astrocytes and Ror2. But the phenotype, function and regulation mechanism of reactive astrocytes remain to be elucidated. In vitro studies, the receptor of C3a (C3aR), a fragment of C3 which marks A1 astrocytes specifically, was found to be regulated by AP-1, which binds in the C3aR promoter region. Interestingly, Wnt5a/Ror2 mediates AP-1 activation. So, we proposed that, after surgery, activated Wnt5a/Ror2 in spinal astrocytes could upregulate AP-1 to increase C3aR transcription, thus stimulating C3 expression and A1 astrocytes to induce chronic post-surgical pain. We plan to use C3aR-/-、Ror2-/- knockout mice to build chronic post-surgical pain model, combining with primary cell and molecular biological techniques like microfluidic quantitative PCR, to study the role of spinal A1 astrocytes in chronic post-surgical pain, and its regulation by Wnt5a/Ror2/AP-1. Our study could provide new idea for targeted prevention of chronic post-surgical pain.