Graduate Program in Biological Sciences, Biochemical Toxicology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Camobi, Santa Maria, RS, 97105-900, Brazil.
Graduate Program in Health Sciences, University of Extreme South Catarinense, Criciúma, SC, Brazil.
Mol Neurobiol. 2020 Oct;57(10):4202-4217. doi: 10.1007/s12035-020-01996-1. Epub 2020 Jul 20.
Fibromyalgia (FM) is one of the most common musculoskeletal pain conditions. Although the aetiology of FM is still unknown, mitochondrial dysfunction and the overproduction of reactive oxygen intermediates (ROI) are common characteristics in its pathogenesis. The reserpine experimental model can induce FM-related symptoms in rodents by depleting biogenic amines. However, it is unclear whether reserpine causes other pathophysiologic characteristics of FM. So far, no one has investigated the relevance of mitochondrial dysfunction in the reserpine-induced experimental FM model using protection- and insult-based mitochondrial modulators. Reserpine (1 mg/kg) was subcutaneously injected once daily for three consecutive days in male Swiss mice. We carried out analyses of reserpine-induced FM-related symptoms, and their modulation by using mitochondrial insult on ATP synthesis (oligomycin; 1 mg/kg, intraperitoneally) or mitochondrial protection (coenzyme Q10; 150 mg/kg/5 days, orally). We also evaluated the effect of reserpine on mitochondrial function using high-resolution respirometry and oxidative status. Reserpine caused nociception, loss in muscle strength, and anxiety- and depressive-like behaviours in mice that were consistent with clinical symptoms of FM, without inducing body weight and temperature alterations or motor impairment. Reserpine-induced FM-related symptoms were increased by oligomycin and reduced by coenzyme Q10 treatment. Reserpine caused mitochondrial dysfunction by negatively modulating the electron transport system and mitochondrial respiration (ATP synthesis) mainly in oxidative muscles and the spinal cord. These results support the role of mitochondria in mediating oxidative stress and FM symptoms in this model. In this way, reserpine-inducing mitochondrial dysfunction and increased production of ROI contribute to the development and maintenance of nociceptive, fatigue, and depressive-like behaviours.
纤维肌痛（FM）是最常见的肌肉骨骼疼痛疾病之一。尽管 FM 的病因仍不清楚，但线粒体功能障碍和活性氧中间体（ROI）的过度产生是其发病机制的共同特征。利血平实验模型通过耗尽生物胺可在啮齿动物中诱导与 FM 相关的症状。然而，利血平是否会导致 FM 的其他病理生理特征尚不清楚。到目前为止，还没有人使用基于保护和损伤的线粒体调节剂研究利血平诱导的实验性 FM 模型中线粒体功能障碍的相关性。利血平（1mg/kg）每天皮下注射一次，连续 3 天。我们进行了利血平诱导的 FM 相关症状分析及其调节，方法是使用对 ATP 合成有损伤作用的线粒体（寡霉素；1mg/kg，腹腔内注射）或线粒体保护剂（辅酶 Q10；150mg/kg/5 天，口服）。我们还使用高分辨率呼吸测定法和氧化状态评估了利血平对线粒体功能的影响。利血平引起了小鼠的痛觉、肌肉力量丧失以及焦虑和抑郁样行为，这些症状与 FM 的临床症状一致，而没有引起体重和体温改变或运动障碍。寡霉素增加了利血平诱导的 FM 相关症状，而辅酶 Q10 治疗则减少了这些症状。利血平通过负调节电子传递系统和线粒体呼吸（ATP 合成）主要在氧化肌肉和脊髓中引起线粒体功能障碍。这些结果支持线粒体在介导该模型中的氧化应激和 FM 症状中的作用。这样，利血平诱导的线粒体功能障碍和 ROI 产量增加导致了痛觉、疲劳和抑郁样行为的发展和维持。
