Comparison of monosodium iodoacetate, medial meniscal transection, and partial medial meniscectomy in vivo rat models of osteoarthritis from the pain and industrial perspective.

Osteoarthritis (OA) is a major global health burden marked by progressive cartilage degeneration and chronic pain with intertwined inflammatory and neuropathic mechanisms. This study compared three rat OA models, monosodium iodoacetate (MIA), medial meniscal transection (MMT), and partial medial meniscectomy (MNX), to assess their translational value, suitability for pharmaceutical research, and identify the most robust and reproducible model for preclinical OA pain research. OA was induced in male Wistar (MIA) or Sprague Dawley (MMT, MNX) rats, and pain progression was evaluated by testing mechanical sensitivity and dynamic weight-bearing. A single oral dose of pregabalin (30 mg/kg) was used for pharmacological validation. The MIA model produced a rapid, robust pain phenotype, with pronounced mechanical hypersensitivity and consistent weight-bearing deficits by day 21. Surgical models progressed more slowly and variably: hypersensitivity emerged by day 21 in MNX rats and by day 49 in MMT rats. Neither surgical model generated stable dynamic weight-bearing deficits, indicating limited sensitivity of current gait-analysis methods for detecting their subtler impairments. Pregabalin reduced mechanical hypersensitivity across all 3 models, confirming their pharmacological validity and utility for analgesic screening. Overall, the MIA model remains the most efficient and reliable for industrial research due to its strong behavioral window, whereas the MNX model offers greater translational relevance if paired with more sensitive and objective behavioral measures. SIGNIFICANCE STATEMENT: By systematically comparing chemical and surgical rat models of osteoarthritis, this study clarifies their strengths and limitations for modeling chronic pain. The results demonstrate that, although the monosodium iodoacetate model delivers robust, reproducible behavioral outcomes, surgical models more accurately reflect disease progression but lack sensitive behavioral readouts. This work informs translational model selection and underscores the need for more objective pain assessment tools.