Notartomaso Serena, Ginerete Roxana Paula, Liberatore Francesca, Nicoletti Ferdinando, Bruno Valeria, Battaglia Giuseppe
Department of Molecular Pathology, Neuropharmacology Unit, I.R.C.C.S. Neuromed, Pozzilli, Italy.
Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.
Mol Pain. 2025 Jan-Dec;21:17448069251367596. doi: 10.1177/17448069251367596. Epub 2025 Aug 2.
Preclinical studies show that vortioxetine displays a robust analgesic activity in models of neuropathic pain. Here, we compared the effect of a 2-week treatment with vortioxetine, duloxetine, amitriptyline, fluoxetine, and paroxetine (all injected i.p. at the daily dose of 10 mg/kg) on mechanical and thermal pain thresholds, risk-taking behaviour and depressive-like behaviour in the streptozotocin (STZ) mouse model of painful diabetic neuropathy. Vortioxetine, duloxetine and amitriptyline reduced mechanical pain in diabetic mice, with vortioxetine displaying the greatest efficacy. In contrast, paroxetine and fluoxetine were inactive. Vortioxetine, duloxetine, amitriptyline and paroxetine were also effective in enhancing thermal pain thresholds in diabetic mice. Induction of diabetes did not affect risk-taking behaviour in the light-dark box test but enhanced depressive-like behaviour in the tail suspension test. All antidepressants, with the exception of amitriptyline, reversed depressive-like behaviour, whereas paroxetine unexpectedly reduced risk-taking behaviour in diabetic mice. We conclude that vortioxetine may offer therapeutic value for alleviating pain in diabetic neuropathy, particularly in patients with comorbid depression.
临床前研究表明，伏硫西汀在神经性疼痛模型中显示出强大的镇痛活性。在此，我们比较了伏硫西汀、度洛西汀、阿米替林、氟西汀和帕罗西汀（均腹腔注射，每日剂量为10mg/kg）为期2周的治疗对链脲佐菌素（STZ）诱导的糖尿病性神经病变小鼠模型的机械性和热痛阈值、冒险行为及抑郁样行为的影响。伏硫西汀、度洛西汀和阿米替林降低了糖尿病小鼠的机械性疼痛，其中伏硫西汀疗效最佳。相比之下，帕罗西汀和氟西汀无效。伏硫西汀、度洛西汀、阿米替林和帕罗西汀在提高糖尿病小鼠热痛阈值方面也有效。糖尿病的诱导并未影响明暗箱试验中的冒险行为，但增强了悬尾试验中的抑郁样行为。除阿米替林外，所有抗抑郁药均逆转了抑郁样行为，而帕罗西汀意外地降低了糖尿病小鼠的冒险行为。我们得出结论，伏硫西汀可能为缓解糖尿病性神经病变的疼痛提供治疗价值，尤其是对于合并抑郁症的患者。
