Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Mol Pain. 2023 Jan-Dec;19:17448069231210423. doi: 10.1177/17448069231210423.
Traumatic neuropathic pain (TNP) is caused by traumatic damage to the somatosensory system and induces the presentation of allodynia and hyperalgesia. Mitochondrial dysfunction, neuroinflammation, and apoptosis are hallmarks in the pathogenesis of TNP. Recently, mitochondria-based therapy has emerged as a potential therapeutic intervention for diseases related to mitochondrial dysfunction. However, the therapeutic effectiveness of mitochondrial transplantation (MT) on TNP has rarely been investigated. Here, we validated the efficacy of MT in treating TNP. Both and TNP models by conducting an L5 spinal nerve ligation in rats and exposing the primary dorsal root ganglion (DRG) neurons to capsaicin, respectively, were applied in this study. The MT was operated by administrating 100 µg of soleus-derived allogeneic mitochondria into the ipsilateral L5 DRG and the culture medium in vitro. Results showed that the viable transplanted mitochondria migrated into the rats' spinal cord and sciatic nerve. MT alleviated the nerve ligation-induced mechanical and thermal pain hypersensitivity. The nerve ligation-induced glial activation and the expression of pro-inflammatory cytokines and apoptotic markers in the spinal cord were also repressed by MT. Consistently, exogenous mitochondria reversed the capsaicin-induced reduction of mitochondrial membrane potential and expression of pro-inflammatory cytokines and apoptotic markers in the primary DRG neurons in vitro. Our findings suggest that MT mitigates the spinal nerve ligation-induced apoptosis and neuroinflammation, potentially playing a role in providing neuroprotection against TNP.
创伤性神经病理性疼痛（TNP）是由躯体感觉系统的创伤性损伤引起的，并导致痛觉过敏和痛觉过敏。线粒体功能障碍、神经炎症和细胞凋亡是 TNP 发病机制的标志。最近，基于线粒体的治疗方法已成为治疗与线粒体功能障碍相关疾病的潜在治疗干预措施。然而，线粒体移植（MT）治疗 TNP 的疗效很少被研究。在这里，我们验证了 MT 治疗 TNP 的疗效。通过在大鼠 L5 脊神经结扎和暴露初级背根神经节（DRG）神经元辣椒素来分别建立 和 TNP 模型，研究了 MT 的疗效。MT 通过将 100µg 比目鱼肌来源的同种异体线粒体注入同侧 L5 DRG 和体外培养基中进行操作。结果表明，有活力的移植线粒体迁移到大鼠脊髓和坐骨神经中。MT 减轻了神经结扎引起的机械和热痛过敏。MT 还抑制了神经结扎引起的脊髓胶质细胞激活以及促炎细胞因子和凋亡标志物的表达。同样，外源性线粒体逆转了辣椒素诱导的初级 DRG 神经元中线粒体膜电位降低以及促炎细胞因子和凋亡标志物的表达。我们的研究结果表明，MT 减轻了脊神经结扎引起的细胞凋亡和神经炎症，可能在提供针对 TNP 的神经保护方面发挥作用。
