Huang Mengjie, Yang Yanyan, Tang Yue, Li Yijie, Wang Xiaohuan, Zhou Mouwang
Department of Rehabilitation Medicine, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China.
Inflammation. 2025 Jul 11. doi: 10.1007/s10753-025-02336-y.
Runt-related transcription factor 1 (RUNX1) is a highly conserved transcription factor involved in immune regulation, inflammation, and nociceptive neuron differentiation. However, its role in central neuropathic pain (CNP) induced by SCI remains unclear. Here, we investigated RUNX1 expression after SCI and its impact on CNP. Using scAAV-mediated RUNX1 knockdown in the spinal cord of SCI rats, we assessed nociceptive behaviors of mechanical allodynia and thermal hyperalgesia by hind paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) before injury and at 21-, 35-, and 49-days post-injury. RUNX1 mRNA and protein levels were analyzed via RT-qPCR and Western blotting, while immunohistochemistry was used to examine its distribution. Our findings revealed that RUNX1 expression was significantly elevated in microglia following SCI. RUNX1 knockdown notably increased PWT and PWL as well as a significant decrease in the aberrant sprouting of nociceptive fibers in SCI rats. Furthermore, in lipopolysaccharide (LPS)-treated BV-2 microglia, RUNX1 knockdown markedly reduced microglial activation and inflammation. A similar reduction in microglial activation and neuroinflammation was observed in SCI rats following RUNX1 knockdown. These findings suggest that RUNX1 contributes to CNP after SCI by promoting microglial activation and neuroinflammation, identifying it as a potential therapeutic target for SCI-induced neuropathic pain.
runt相关转录因子1（RUNX1）是一种高度保守的转录因子，参与免疫调节、炎症和伤害性神经元分化。然而，其在脊髓损伤（SCI）诱导的中枢神经性疼痛（CNP）中的作用仍不清楚。在此，我们研究了SCI后RUNX1的表达及其对CNP的影响。通过在SCI大鼠脊髓中使用scAAV介导的RUNX1敲低，我们在损伤前以及损伤后21天、35天和49天，通过后爪撤离阈值（PWT）和爪撤离潜伏期（PWL）评估了机械性异常性疼痛和热痛觉过敏的伤害性反应行为。通过RT-qPCR和蛋白质印迹分析RUNX1 mRNA和蛋白质水平，同时使用免疫组织化学检查其分布。我们的研究结果显示，SCI后小胶质细胞中RUNX1表达显著升高。RUNX1敲低显著增加了SCI大鼠的PWT和PWL，同时伤害性纤维的异常出芽也显著减少。此外，在脂多糖（LPS）处理的BV-2小胶质细胞中，RUNX1敲低显著降低了小胶质细胞的激活和炎症。在RUNX1敲低后的SCI大鼠中也观察到小胶质细胞激活和神经炎症的类似减少。这些发现表明，RUNX1通过促进小胶质细胞激活和神经炎症而导致SCI后的CNP发生，确定其为SCI诱导的神经性疼痛的潜在治疗靶点。
