Effect of resveratrol on the cartilage and nociceptive system of Osteoarthritic animals
S. Rosas1,2,3,, , T. Aguiar1,2,3, L. Almeida1,2,3, D. Nascimento1,2,3, S. Adães1,2,3, J.M. Castro-Lopes1,2,3, F.L. Neto1,2,3, J. Ferreira-Gomes1,2,3
1 Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal
2 Pain Research Group, Institute for Molecular and Cell Biology (IBMC), Porto, Portugal
3 i3S - Institute for Investigation and Innovation in Health, Porto, Portugal

Aim: This study aims to evaluate the effect of RV on the nociceptive behavior, histopathological alterations at the knee and DRG neurons of OA rats.

Introduction: Osteoarthritis (OA) is a common degenerative joint disease and arthritic pain is a prominent symptom associated with reduced quality of life. Peripheral pain mechanisms seem to be involved, with cartilage lesions showing a repercussion in Dorsal Root Ganglia (DRG) neurons. Resveratrol, a polyphenol with proven anti-inflammatory, anti-oxidant and neuroprotective properties, has been shown to prevent development of OA and act as an antinociceptive agent. However, its systemic effects once the disease has fully developed remain unclear.

Methods: To evaluate this, OA was induced in 18 male Wistar rats through intra-articular injection of mono-iodoacetate (MIA) (day 0). Animals were allowed to develop the disease for two weeks, after which followed a 4-week-long treatment with resveratrol or vehicle, administered intraperitoneally twice daily (10mg/kg). Nociceptive behavior was quantified weekly using the CatWalk and Knee-Bend tests. Animals were sacrificed one week after the last treatment administration, their knees were dissected for histopathological analysis, and the DRG were dissected and processed for immunohistochemical evaluation of activating transcription factor 3 (ATF-3) neuronal expression.

Results: Resveratrol was unable to prevent cartilage degeneration but it significantly decreased ATF-3 expression. The nociceptive behavior of OA animals treated with resveratrol decreased during the first three weeks of treatment, in comparison to day 14 (before treatment was initiated), as shown by Knee-Bend scores. However, this tendency reverted as the disease progressed.

Conclusion: These results indicate that resveratrol may have antinociceptive effects in the early stages of the disease development, but it might not play such a relevant role once the disease has progressed. Thus, further studies are needed to fully understand the possible role of resveratrol in the different stages of OA.

Acknowledgements: The study was supported by the Chair on Pain Medicine of the Faculty of Medicine, University of Porto and by the Grünenthal Foundation – Portugal. By the time the study was conducted DN was receiving a doctoral grant (SFRH/BD/79497/2011) by Fundação para a Ciência e a Tecnologia (FCT), Portugal and SA had a doctoral grant by Fundação Calouste Gulbenkian, Portugal.

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