Abstract
Background and Purpose: Treatment of osteoarthritis (OA) pain
often yields unsatisfactory results, making the search for new
pain-relieving options essential. Vortioxetine, an antidepressant with a
unique mechanism of action, has recently shown analgesic properties. We
aimed to investigate its effects in the OA model and gain insight into
the underlying molecular mechanisms. Duloxetine (a second-line drug for
pain relief in OA) was studied as a reference.
Experimental Approach: In the monoiodoacetate (MIA)-induced
model of knee OA in rats of both sexes, pain-related behaviour was
assessed in weight-bearing and von Frey tests. Antidepressants were
administered orally once daily for 28 days. Gene expression of
pain-related mediators (Ngf , Il-1β , Tnf-α ,Bdnf , and Tac1 encoding substance P) and oxidative stress
parameters were determined after completion of the treatment/behavioural
testing protocol.
Key results: Vortioxetine dose-dependently reduced
weight-bearing asymmetry and mechanical allodynia of the paw ipsilateral
to the MIA-injected knee. Duloxetine was also effective. Vortioxetine
reduced the increased Ngf mRNA expression in the MIA-injected
knees to the level observed in the sham-injected counterparts. It also
reduced oxidative stress parameters in the affected knees, more
effectively in females than in males. Duloxetine showed no effect on
locally increased Ngf mRNA expression and oxidative stress. Both
antidepressants decreased mRNA expression of pain-related mediators in
the lumbar L3-L5 ipsilateral DRGs and spinal cords, which were
upregulated in MIA-injected rats. This effect was male-specific.
Conclusion and Implications: Vortioxetine may be effective
against chronic pain in OA. This effect appears to be mediated, at least
in part, by normalization of NGF expression in the affected joint.
Key words: osteoarthritis pain, vortioxetine, duloxetine, nerve
growth factor (NGF), oxidative stress, sex differences