Background. Osteoarthritis is the leading cause of chronic joint pain, causing important productivity and economic losses. It is believed that peripheral and centralized sensitization play a role in the creation and maintenance of a chronic painful state. Different animal models have been employed for the investigation of pain mechanisms and evaluation of potential treatments, but none of them are ideal in terms of reproducibly, reliability and translational value. Methods. In the search for better animal model, this pilot study was performed with the goal of evaluating pain functional outcomes and spinal biomarkers between three surgical rat models of osteoarthritic pain, i.e. destabilization of the medial meniscus, cranial cruciate ligament transection and the combination of both, and comparing those results to the intra-articular injection of monosodium iodoacetate. Six rats were assigned to each model group and a Sham group. Static weight bearing, punctate tactile paw withdrawal threshold, and spinal neuropeptides (substance P, calcitonin gene-related peptide, bradykinin, and somatostatin) were evaluated for each group. Results. Both the monosodium iodoacetate and combination models induced functional alterations in static weight bearing and punctate tactile paw withdrawal threshold, the changes being more persistent in the combination group. Both also produced an increased release of pro-nociceptive and anti-nociceptive neuropeptides at different time-points. When surgical models were compared, the cranial cruciate ligament transection and destabilization of the medial meniscus models were less interesting, with temporary functional alterations, and no significant change in neuropeptides. Discussion. The surgical induction of osteoarthritis was accompanied by quantifiable neurophysiologic changes relating to non-physiologic pain. Comparison with the monosodium iodoacetate model showed that the interest of a surgical model, especially the combination of destabilization of the medial meniscus and cranial cruciate ligament transection, might reside in more persistent and progressive changes, a model that may represent better the human post-traumatic osteoarthritis.
Macrophage Phenotypes are Associated With Processes of Osteoarthritis in The Collagenase-Induced Osteoarthritis (CIOA) and Destabilization of The Medial Meniscus (DMM) Mouse Models
