骨癌痛疼痛剧烈现有镇痛方法有限，原因是其机制目前尚未明了，转录组学在慢性疼痛中的作用日益瞩目。前期，我们通过acRIP-seq等技术发现：RNA ac4C修饰酶NAT10表达上调，且骨癌大鼠脊髓背角突触前膜黏附分子Neurexin2 mRNA ac4C及Neurexin2的表达均明显上调；抑制NAT10或Neurexin2均可缓解骨癌痛。据此提出研究假设：骨癌导致脊髓神经元NAT10介导Neurexin2 mRNA ac4C，促进Neurexin2 mRNA稳定和蛋白表达，使脊髓突触的结构和功能改变，从而参与骨癌痛的发生。为验证该假设，本项目将在多个水平上研究Neurexin2 mRNA ac4C与Neurexin2表达的关系，以及其对骨癌大鼠脊髓突触可塑性的影响。本项目的顺利实施将有助于揭示Neurexin2 mRNA ac4C参与骨癌痛脊髓敏化的机制，为临床治疗骨癌痛提供新的理论依据。

Cancer-induced bone pain is so severe and hard to control. The reason is that its mechanism is still unclear. The role of transcriptomics in the development of chronic pain is getting more and more attention. Our preliminary study through acRIP-seq and other technologies showed that the expression of RNA ac4C modification enzyme NAT10, presynaptic membrane neuroadhesion molecule neurexin2 mRNA acetylation and neurexin2 all were significantly up-regulated in rats with bone cancer pain; Inhibition of NAT10 or neurexin2 could both alleviate bone cancer hyperalgesia. Based on these exciting preliminary data, we suppose that bone cancer causes spinal NAT10 to mediate neurexin2 mRNA ac4C, promotes the stability of neurexin2 mRNA and the expression of neurexin2, enhances structural and functional changes in spinal cord synapses, and thus participating in the development of cancer bone pain. To test the hypothesis, this research project plans to investigate the regulatory relationship of neurexin2 mRNA ac4C and neurexin2 and their role in bone cancer pain through a multilevel point, and to influence the spinal synaptic plasticity in bone cancer rats. The successful implementation of this project will reveal the mechanism of neurexin2 mRNA ac4C involved in spinal sensitization of bone cancer pain, and provide a new theoretical basis for clinical treatment of bone cancer pain.