Détection et validation de marqueurs épigénétiques d’atteinte nociceptive dans l’arthrose sur modèle expérimental murin
Osteoarthritis (OA) is considered the most common cause of chronic joint pain in humans, but also in companion animal patients. Nociceptive sensitization has been extensively associated with the disease. However, the pathological mechanisms leading to the development of this degenerative joint disease remain only partially understood. In the past few years, surgical induction of OA in rats allowed us to characterize some modifications in functional pain behaviors and to quantify neurophysiological changes. Hence, it has now been suggested that epigenetic mechanisms could also take part in OA physiopathology. The goal of this project was to validate a panel of different pain evaluation methods in a surgically-induced OA rat model with the objective of a better understanding of OA pain. To achieve this, previously validated structural and functional pain assessments were conducted, as well as neuropeptidomic analysis. To test the contribution of epigenetic modification in OA, differential expression of spinal miRNAs was validated by RT-qPCR. The surgical intervention led to the progression of significant structural damages. Moreover, this model confirmed the central nociceptive sensitization development in the OA rats. Indeed, changes in functional behaviors and in neuropeptidomic expression were identified. These findings were interestingly accompanied by an enhanced expression of miR-181b, a micro-RNA previously linked to endogenous control of pain. Multiple pain determinants were taken into account in this surgically-induced OA model; therefore, this study contributed to the advancement of knowledge in chronic pain translational research. This project highlights the relevance of neuro-epigenetics in OA pain studies.
Neuropeptides Chronic pain Osteoarthritis Animal model Biomarkers Epigenetics Micro-RNA Neuropeptides Functional evaluations