Vortioxetine reduced the expression of pain-related mediators in the DRGs and spinal cord of male rats with MIA-injected knees
Intra-articular injection of MIA significantly increased mRNA levels ofIl-1β , Tnf-α , Ngf , Bdnf and substance P encoding Tac1 gene in the ipsilateral L3-L5 DRGs compared with saline control in both males and females (all post-hoc P ≤ 0.045; Figure 6A and Supplementary Figure 2A). Prolonged 4-week treatment with vortioxetine (2 mg/kg/day) and duloxetine (15 mg/kg/day) significantly decreased mRNA expression of all mediators examined compared with the MIA control in male rats (all post-hoc P ≤ 0.020; Figure 6A). In female rats the expression-suppressing effect of the antidepressants was not observed (all post-hoc P ≥ 0.130; Supplementary Figure 2A).
Similarly, MIA-treated animals of both sexes exhibited significantly increased expression of Il-1β , Tnf-α , Bdnf and substance P (Tac1 ) in the L3-L5 segment of the spinal cord, compared with saline-treated animals (all post-hoc P ≤ 0.040; Figure 6B and Supplementary Figure 2B). Treatment with vortioxetine (2 mg/kg/day) and duloxetine (15 mg/kg/day) for 28 days significantly decreased Il-1β , Tnf-α , Bdnf and substance P (Tac1 ) mRNA levels in the spinal cord of male rats (all post-hoc P ≤ 0.030; Figure 6B). In female rats, antidepressants only reduced the expression of substance P (Tac1 ) (post-hoc P < 0.001 in both groups; Supplementary Figure 2B).