University of Belgrade - Faculty of Pharmacy, Department of Pharmacology, Belgrade, Serbia.
University of Belgrade - Faculty of Pharmacy, Department of Pharmacology, Belgrade, Serbia.
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Dec 20;103:109975. doi: 10.1016/j.pnpbp.2020.109975. Epub 2020 May 25.
Chronic pain and depression commonly occur together so dual-acting agents might be particularly useful. The population of patients with chemotherapy-induced neuropathy is increasing in parallel with the increase of population of cancer survivors and there is a compelling need for satisfactory treatment of symptoms of neuropathy and concomitant depression. We examined the effects of vortioxetine, a novel antidepressant with unique mechanism of action, on pain hypersensitivity and depression-like behavior in oxaliplatin-induced neuropathy model in mice (OIPN). Vortioxetine (1-10 mg/kg, p.o.) significantly and dose-dependently reduced mechanical allodynia in von Frey test and cold allodynia in acetone test in OIPN mice, in both repeated prophylactic and acute therapeutic treatment regimens. It also reduced depression-like behavior in the forced swimming test in OIPN mice, in both treatment paradigms. Its antiallodynic and antidepressive-like effects were comparable to those exerted by duloxetine (1-15 mg/kg, p.o.). The antiallodynic and antidepressive-like effects of repeatedly administered vortioxetine might be related to the increased content of 5-hydroxytryptamine (5-HT) and noradrenaline (NA), detected in the brainstem of treated OIPN mice. These results indicate that vortioxetine could be potentially useful in prevention and treatment of chemotherapy-induced neuropathy, for the relief of pain and concomitant depressive symptoms. It should be further tested to this regard in clinical settings.
慢性疼痛和抑郁常同时发生，因此双重作用的药物可能特别有用。随着癌症幸存者人数的增加，化疗引起的周围神经病变患者人数也在增加，因此迫切需要令人满意地治疗神经病变和伴随的抑郁症状。我们研究了具有独特作用机制的新型抗抑郁药文拉法辛（vortioxetine）对奥沙利铂诱导的周围神经病变模型（OIPN）中小鼠痛觉过敏和抑郁样行为的影响。文拉法辛（1-10mg/kg，po）在奥沙利铂诱导的周围神经病变小鼠中，在反复预防性和急性治疗方案中，均显著且呈剂量依赖性地降低von Frey 试验中的机械性痛觉过敏和丙酮试验中的冷痛觉过敏。它还降低了奥沙利铂诱导的周围神经病变小鼠强迫游泳试验中的抑郁样行为，在两种治疗方案中均如此。其抗痛觉过敏和抗抑郁样作用与度洛西汀（1-15mg/kg，po）相当。反复给予文拉法辛的抗痛觉过敏和抗抑郁样作用可能与治疗后的 OIPN 小鼠脑干中 5-羟色胺（5-HT）和去甲肾上腺素（NA）含量增加有关。这些结果表明，文拉法辛可能对预防和治疗化疗引起的周围神经病变、缓解疼痛和伴随的抑郁症状有用。在临床环境中应进一步对此进行测试。
