PWT, paw withdrawal threshold; TOS, total pro-oxidant status; O₂^•-, superoxide anion radical; PAB, prooxidant-antioxidant balance; AOPP, advanced oxidation protein products; MDA, malondialdehyde.

Prolonged 28-day administration of vortioxetine (2 and 10 mg/kg/day) and duloxetine (15 and 25 mg/kg/day) significantly and dose-dependently reduced the MIA-induced weight-bearing deficit at the injured limb (allpost-hoc P ≤ 0.015 for time-course data and allpost-hoc P ≤ 0.009 for AUC values; Figure 2). Both antidepressants also caused significant and dose-dependent anti-allodynic effects in rats with OA, as manifested by an increase in paw withdrawal thresholds and AUC values (all post-hoc P< 0.001; Figure 3). There was no sex difference in the magnitude of effects in either vortioxetine- or duloxetine-treated groups in weight-bearing test (all AUC post-hoc P ≥ 0.360; Supplementary Table 2). In the von Frey test, no difference in the anti-allodynic effects of vortioxetine was observed between male and female rats, whereas a slightly more pronounced response to duloxetine was observed in male rats for both doses (AUC post-hoc P = 0.001; Supplementary Table 2).

Neither treatment with vortioxetine (2 and 10 mg/kg/day) nor with duloxetine (15 and 25 mg/kg/day) significantly affected the time rats spent on the rotarod (all post-hoc P ≥ 0.273; Supplementary Figure 1).