Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain

• Published in: Biomedicines Vol. 11; no. 4; p. 1137
• Main Authors: Turan Yücel, Nazlı, Kandemir, Ümmühan, Üçel, Umut İrfan, Demir Özkay, Ümide, Can, Özgür Devrim
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2023; MDPI
• Subjects: Acetylcholine receptors (muscarinic); Adrenergic receptors; allodynia; Animals; Atropine; c-Fos protein; Diabetes; Diabetes mellitus; Diabetic neuropathy; Dopamine; Dopamine D2 receptors; Dorsal horn; Drug dosages; Drug withdrawal; dynamic plantar test; Experiments; FDA approval; Glucose; Hyperalgesia; Motor ability; Nervous system; Pain; Pain perception; Randall–Selitto test; Serotonin; Streptozocin; Sulpiride; vortioxetine; Yohimbine; United States; United States > US; Italy; Turkey; allodynia; hyperalgesia; diabetes; dynamic plantar test; vortioxetine; Randall–Selitto test
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11041137

The therapeutic potential of vortioxetine on mechanical hyperalgesia/allodynia was investigated in rats with streptozotocin-induced diabetes, and its possible mechanism of action was elucidated in this study. The obtained findings demonstrated that subacute vortioxetine treatment (5 and 10 mg/kg for 2 weeks) increased the reduced paw-withdrawal thresholds of diabetic rats both in the Randall-Selitto and Dynamic plantar tests. Moreover, the falling latencies of animals did not change in the Rota-rod assessments. These results suggest that vortioxetine administration significantly improved diabetes-induced hyperalgesia and allodynia responses in the rats without affecting their motor coordination. The vortioxetine (5 mg/kg)-induced antihyperalgesic and antiallodynic effects were reversed by AMPT, yohimbine, ICI 118,551, sulpiride and atropine pre-treatments, suggesting the involvement of the catecholaminergic system, α - and β -adrenoceptors, D dopaminergic receptors and cholinergic muscarinic receptors in the exhibited pharmacological activity, respectively. Moreover, the data from the immunohistochemical studies indicated that the inhibition of c-Fos overexpression in dorsal horn neurons also mediates the beneficial effect of this drug. Vortioxetine induced no difference in plasma glucose levels in diabetic rats. If clinical studies confirm these findings, the concomitant beneficial effect of vortioxetine on mood disorders and its neutral activity profile on glycemic control may make it an alternative drug for the treatment of neuropathic pain.