Comprehensive Evaluation of Long-term Dynamic Mechanical Behavior in a Rat MIA OA Model

Osteoarthritis (OA) is highly prevalent across the world with 30% of the US population who are 45 and older estimated to have knee osteoarthritis. The primary clinical indication of OA is pain. Mono-iodo acetate (MIA) induced osteoarthritis is commonly used to study pain in pre-clinical models. Currently mechanical allodynia and thermal hyperalgesia are used to measure the pain outcomes in most pre-clinical models however, the non-evoked dynamic weight bearing analysis provides more clinically relevant behavioral assessment of pain. The goal of the study is to comprehensively understand the changes in dynamic weight bearing behavior of rats with MIA induced OA over a period of 16 weeks. Osteoarthritis was induced in female Sprague-Dawley rats by C-arm guided injections of MIA (3 mg) into the intra-articular region of the right knee. Non-evoked dynamic weight bearing was evaluated using a pressure sensor system (Bioseb DWB 2.0), mechanical allodynia using Von Frey filaments, and transcriptional changes at the dorsal root ganglion using BioRad gene array. MIA model showed mechanical allodynia of the ipsilateral paw for over 3 months. The dynamic weight bearing parameters reveal continuous compensatory weight preference towards the uninjured limbs for the same period. Unlike Von Frey, significantly different dynamic behavioral parameters begin to appear within 24 hours post MIA injection. Moreover, parameters related to weight and area distribution showed temporal changes over the course of the study. The study shows that dynamic weight bearing assessment is an effective tool to understand the long-term progression of pain behavior in a MIA model. Grant support from NIH R01AR075143.