Oxaliplatin (OXA) is an antineoplastic agent used for the treatment of cisplatin-resistant tumours, presenting lower incidence of nephrotoxicity and myelotoxicity than other platinum-based drugs. However, OXA treatment is highly associated with painful peripheral neuropathy, a well-known and relevant side effect caused by mitochondrial dysfunction. The transfer of functional exogenous mitochondria (mitotherapy) is a promising therapeutic strategy for mitochondrial diseases. We investigated the effect of mitotherapy on oxaliplatin-induced painful peripheral neuropathy (OIPN) in male mice. OIPN was induced by i.p. injections of oxaliplatin (3 mg/kg) over 5 consecutive days. Mechanical (von Frey test) and cold (acetone drop test) allodynia were evaluated between 7 and 17 days after the first OXA treatment. Mitochondria was isolated from donor mouse livers and mitochondrial oxidative phosphorylation was assessed with high resolution respirometry. After confirming that the isolated mitochondria were functional, the organelles were administered at the dose of 0.5 mg/kg of mitochondrial protein on days 1, 3 and 5. Treatment with OXA caused both mechanical and cold allodynia in mice that were significant 7 days after the initial injection of OXA and persisted for up to 17 days. Mitotherapy significantly prevented the development of both sensory alterations, and attenuated body weight loss induced by OXA. Mitotherapy also prevented spinal cord ERK1/2 activation, microgliosis and the increase in TLR4 mRNA levels. Mitotherapy prevented OIPN by inhibiting neuroinflammation and the consequent cellular overactivity in the spinal cord, presenting a potential therapeutic strategy for pain management in oncologic patients undergoing OXA treatment.

奥沙利铂（OXA）是一种抗肿瘤药物，用于治疗顺铂耐药肿瘤，与其他铂类药物相比，肾毒性和骨髓毒性发生率较低。然而，OXA 治疗与疼痛性周围神经病高度相关，这是一种众所周知的由线粒体功能障碍引起的相关副作用。功能性外源线粒体的转移（线粒体疗法）是线粒体疾病的一种有前途的治疗策略。我们研究了线粒体疗法对雄性小鼠奥沙利铂诱导的疼痛性周围神经病 (OIPN) 的影响。OIPN 是通过连续 5 天腹腔注射奥沙利铂 (3 mg/kg) 诱导的。在第一次 OXA 治疗后 7 至 17 天评估机械性（冯弗雷试验）和冷性（丙酮滴试验）异常性疼痛。从供体小鼠肝脏中分离线粒体，并用高分辨率呼​​吸测定法评估线粒体氧化磷酸化。确认分离的线粒体具有功能后，在第 1、3 和 5 天以 0.5 mg/kg 线粒体蛋白的剂量对细胞器进行给药。 OXA 治疗引起小鼠机械性和冷性异常性疼痛，这种疼痛在治疗后 7 天更为明显。首次注射 OXA，持续长达 17 天。线粒体疗法显着阻止了感觉改变的发展，并减弱了 OXA 引起的体重减轻。线粒体疗法还可以防止脊髓 ERK1/2 激活、小胶质细胞增生和 TLR4 mRNA 水平增加。线粒体疗法通过抑制神经炎症和随之而来的脊髓细胞过度活动来预防 OIPN，为接受 OXA 治疗的肿瘤患者的疼痛管理提供了一种潜在的治疗策略。