Deng Yi-Fan, Xiang Ping, Du Jing-Yi, Liang Jian-Fen, Li Xiang
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Department of Medical Quality Management, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
Neural Regen Res. 2023 Feb;18(2):456-462. doi: 10.4103/1673-5374.346547.
Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model. However, the role of ferroptosis in inflammatory pain remains inconclusive. Therefore, we aimed to explore whether ferroptosis in the spinal cord and dorsal root ganglion contributes to complete Freund's adjuvant (CFA)-induced painful behaviors in rats. Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats. These changes included iron overload, enhanced lipid peroxidation, disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels, and abnormal morphological changes in mitochondria. Intrathecal treatment of liproxstatin-1 (a ferroptosis inhibitor) reversed these ferroptosis-related changes and alleviated mechanical and thermal hypersensitivities in CFA rats. Our study demonstrated the occurrence of ferroptosis in the spinal cord and dorsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of ferroptosis inhibitors, such as liproxstatin-1, is a potential therapeutic strategy for treating inflammatory pain.
先前的研究已经证实了铁依赖性铁死亡与周围神经损伤诱导的神经病理性疼痛模型之间的关系。然而，铁死亡在炎性疼痛中的作用仍无定论。因此，我们旨在探究脊髓和背根神经节中的铁死亡是否会导致弗氏完全佐剂（CFA）诱导的大鼠疼痛行为。我们的结果显示，各种生化和形态学变化与CFA大鼠脊髓和背根神经节组织中的铁死亡有关。这些变化包括铁过载、脂质过氧化增强、抗酰基辅酶A合成酶长链家族成员4和谷胱甘肽过氧化物酶4水平紊乱以及线粒体形态异常变化。鞘内注射liproxstatin-1（一种铁死亡抑制剂）可逆转这些与铁死亡相关的变化，并减轻CFA大鼠的机械性和热超敏反应。我们的研究证明了在炎性疼痛的啮齿动物模型中脊髓和背根神经节组织中存在铁死亡，并表明鞘内给予铁死亡抑制剂（如liproxstatin-1）是治疗炎性疼痛的一种潜在治疗策略。
