EXPRESS: Comparative study on the analgesic effect of vortioxetine and other antidepressants in the streptozotocin mouse model of painful diabetic neuropathy

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.