Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.
Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China.
Mol Pain. 2023 Jan-Dec;19:17448069231190815. doi: 10.1177/17448069231190815.
Neuropathic pain (NP) occurs frequently in the general population and has a negative impact on the quality of life. There is no effective therapy available yet owing to the complex pathophysiology of NP. In our previous study, we found that urolithin A (UA), a naturally occurring microflora-derived metabolite, could relieve NP in mice by inhibiting the activation of microglia and release of inflammation factors. Here in this study, we sought to investigate whether mitophagy would be activated when UA alleviated NP in mice. We showed that the autophagy flow was blocked in the spinal dorsal horn of the chronic constriction injury (CCI) mice when the most obvious pain behavior occurs. Intraperitoneal injection of UA markedly activated the mitophagy mediated by PTEN-induced kinase 1/Parkin, promoted mitobiogenesis in both neurons and microglia, and alleviated NP in the CCI mice. In summary, our data suggest that UA alleviates NP in mice and meanwhile induces mitophagy activation, which highlights a therapeutic potential of UA in the treatment of NP.
神经病理性疼痛（NP）在普通人群中经常发生，对生活质量有负面影响。由于 NP 的病理生理学复杂，目前尚无有效的治疗方法。在我们之前的研究中，我们发现尿石素 A（UA），一种天然存在的微生物衍生代谢物，通过抑制小胶质细胞的激活和炎症因子的释放，可减轻小鼠的 NP。在本研究中，我们试图探讨 UA 减轻小鼠 NP 时是否会激活自噬。我们表明，在最明显的疼痛行为发生时，慢性缩窄性损伤（CCI）小鼠的脊髓背角中的自噬流被阻断。UA 的腹腔注射可显著激活 PTEN 诱导的激酶 1/ Parkin 介导的线粒体自噬，促进神经元和小胶质细胞中的线粒体生物发生，并减轻 CCI 小鼠的 NP。总之，我们的数据表明 UA 可减轻小鼠的 NP，并同时诱导自噬激活，这突出了 UA 在治疗 NP 方面的治疗潜力。
