慢性术后疼痛是一种常见的手术并发症，严重影响患者生存质量和预后，具体发生机制尚不明确。申请人前期研究发现围术期睡眠节律紊乱加重神经病理性疼痛。预实验又发现围术期睡眠节律紊乱可加重小鼠术后疼痛，伴有m6A甲基化转移酶WTAP的表达上调；进一步研究提示WTAP可调控Drp1介导的线粒体分裂融合过程以及脊髓钟基因Per1的表达；而Per1参与调控Drp1表达及活性。由此我们提出假说：围术期睡眠节律紊乱可能通过m6A甲基化修饰影响钟基因Per1的表达，从而导致Drp1介导的线粒体分裂融合障碍，进而诱发慢性术后疼痛。本项目拟以切口痛小鼠为模型，通过干预小鼠围术期睡眠节律，从分子-细胞-整体水平研究m6A甲基化修饰对线粒体分裂融合的调控作用，并从外周钟基因角度探索其相关机制，深入探讨睡眠节律紊乱在术后疼痛的作用。研究结果有利于揭示慢性术后疼痛发生发展的新机制，为临床防治慢性术后疼痛提供新的理论依据。

Chronic post-surgical pain (CPSP) is one of the most common complications after surgery. The quality of life and the prognosis of these patients are seriously affected. However, the mechanism remains unclear. Our previous study indicated that sleep-awake rhythm disorders worsened neuropathic pain. Our pre-experiment results suggested that disturbing the natural sleep-awake rhythm could also aggravate postoperative pain, with the upregulation of m6A methyltransferase WTAP. Further study showed the increased expression of Drp1 and Per1 could be modulated by WTAP. Furthermore, the expression of Drp1 was influenced by Per1. Thus we concluded the hypothesis that the abnormal sleep-awake rhythm in the perioperative period could regulate the expression of Per1 through the modification of m6A, which results in the mitochondrial fission and fusion and further participates in CPSP. This study aims to explore the role of m6A RNA methylation in mitochondrial fission and fusion in CPSP induced by the abnormal sleep-awake rhythm in vivo and in vitro. This study are expected to reveal the risky factors related to CPSP and the mechanism underlying it from a new point of view, and provide a new strategy in the clinical prevention and treatment for CPSP.