Vortioxetine reduces the development of pain-related behaviour in a knee osteoarthritis model in rats: Involvement of nerve growth factor (NGF) down-regulation
Maja Tomić, Katarina Nastić, Miroslav Dinić, Emilija Brdarić, Jelena Kotur-Stevuljević, Uroš Pecikoza, David Pavićević, Ana Micov, Danijela Milenković, Aleksandar Jovanović, Radica Stepanović-Petrović
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引用次数: 0
Abstract
Background and Purpose
Vortioxetine, a multimodal-acting antidepressant, has recently shown analgesic properties. We aimed to investigate its prophylactic effect in the osteoarthritis (OA) model and gain insights into the underlying molecular mechanisms. Duloxetine was studied as a reference.
Experimental Approach
In the monoiodoacetate (MIA)-induced rat model of knee OA, 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 and duloxetine dose dependently reduced weight-bearing asymmetry and mechanical hyperalgesia of the paw ipsilateral to the MIA-injected knee. Vortioxetine reduced the increased Ngf mRNA expression in the MIA-injected knees to the level in sham-injected counterparts. It reduced oxidative stress parameters in the affected knees, more effectively in females than males. Duloxetine showed no effect on 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 up-regulated in MIA-injected rats. This effect was male-specific.
Conclusion and Implications
Vortioxetine may be effective against the development of chronic pain in OA. Its antihyperalgesic effect may be mediated, at least in part, by normalization of NGF expression in the affected joint. Decrease of localized oxidative stress and of expression of pain-related mediators that contribute to central sensitization are also involved in vortioxetine's antihyperalgesic effect, in a sex-specific pattern.
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.