Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland.
Molecules. 2021 Apr 20;26(8):2398. doi: 10.3390/molecules26082398.
Fibromyalgia is a disease characterized by lowered pain threshold, mood disorders, and decreased muscular strength. It results from a complex dysfunction of the nervous system and due to unknown etiology, its diagnosis, treatment, and prevention are a serious challenge for contemporary medicine. Impaired serotonergic and dopaminergic neurotransmission are regarded as key factors contributing to fibromyalgia. The present research assessed the effect of serotonergic and dopaminergic system modulators (vortioxetine and ropinirole, respectively) on the pain threshold, depressive-like behavior, anxiety, and motor functions of mice with fibromyalgia-like symptoms induced by subcutaneous reserpine (0.25 mg/kg). By depleting serotonin and dopamine in the mouse brain, reserpine induced symptoms of human fibromyalgia. Intraperitoneal administration of vortioxetine and ropinirole at the dose of 10 mg/kg alleviated tactile allodynia. At 5 and 10 mg/kg ropinirole showed antidepressant-like properties, while vortioxetine had anxiolytic-like properties. None of these drugs influenced muscle strength but reserpine reduced locomotor activity of mice. Concluding, in the mouse model of fibromyalgia vortioxetine and ropinirole markedly reduced pain. These drugs affected emotional processes of mice in a distinct manner. Hence, these two repurposed drugs should be considered as potential drug candidates for fibromyalgia. The selection of a specific drug should depend on patient's key symptoms.
纤维肌痛症是一种以疼痛阈值降低、情绪障碍和肌肉力量下降为特征的疾病。它是由神经系统的复杂功能障碍引起的,由于其病因不明,其诊断、治疗和预防是当代医学的一个严峻挑战。血清素能和多巴胺能神经递质传递受损被认为是导致纤维肌痛症的关键因素。本研究评估了血清素能和多巴胺能系统调节剂(分别为文拉法辛和罗匹尼罗)对皮下利血平(0.25mg/kg)诱导的具有纤维肌痛样症状的小鼠的疼痛阈值、抑郁样行为、焦虑和运动功能的影响。通过耗尽小鼠大脑中的血清素和多巴胺,利血平诱导出人类纤维肌痛的症状。文拉法辛和罗匹尼罗以 10mg/kg 的剂量腹腔给药可缓解触觉过敏。5mg/kg 和 10mg/kg 的罗匹尼罗表现出抗抑郁样作用,而文拉法辛具有抗焦虑样作用。这些药物都不影响肌肉力量,但利血平降低了小鼠的运动活性。综上所述,在纤维肌痛症的小鼠模型中,文拉法辛和罗匹尼罗显著减轻了疼痛。这些药物以不同的方式影响了小鼠的情绪过程。因此,这两种再利用药物应被视为纤维肌痛症的潜在候选药物。特定药物的选择应取决于患者的主要症状。