Monoiodoacetate (MIA) Model of Osteoarthritis Pain

Musculoskeletal disorders represent the fourth most common cause of disability in both developed and developing countries. Osteoarthritis (OA) and, to a lesser extent, rheumatoid arthritis (RA) are considered to be the most common of the articular disorders and are frequently cited as the leading cause of persistent musculoskeletal pain. Osteoarthritis (OA) is a degenerative joint disease that affects a majority of the elderly population causing chronic pain and joint disability. Animal models of OA commonly used are based on the histopathological similarities to human disease and thus are focused on the study of the pathogenesis of cartilage degeneration, either naturally occurring or chemically or surgically induced.

In the model proposed by Transpharmation in mice and rats, a single intra-articular injection of monoiodoacetate (MIA) into the femorotibial joint produces progressive joint degeneration through inhibition of glycolysis and subsequent chondrocyte death that develops over several weeks. Weight bearing is assessed to reveal the analgesic potency of test compounds during both early and late phases of the development of the model.

Monoiodoacetate (MIA)

Intra-articular injection of Monoiodoacetate
Primary species: Mouse (0.5mg in 5µl) & Rat (2mg in 25µL)
Primary readout: Weight bearing
Positive control: Celecoxib (early phase) and Pregabalin (late phase)
Recommended N of 10

Rat: Early phase design
Early phase timeline. MIA injected intra-articularly on day 0; weight bearing on day 3, then compound dosing at T = 0 with weight bearing at 1 and 2 hours; compound dosed once daily from day 4 to day 7, with weight bearing at 1 and 2 hours on days 5 and 7. Line chart of ipsi/contra weight bearing (%) from baseline to day 7 at 1 and 2 hours after dosing, for sham, vehicle, celecoxib 50 mg/kg and pregabalin 30 mg/kg groups. Celecoxib restores weight bearing with daily dosing on days 3 to 7.
Rat: Late phase design
Late phase timeline. MIA injected intra-articularly on day 0; weight bearing on day 3; compound dosed once daily from day 24 to day 28, with weight bearing at 1 and 2 hours on days 24, 26 and 28. Line chart of ipsi/contra weight bearing (%) from baseline to day 28, with 1 and 2 hour readings on days 24, 26 and 28. Pregabalin restores weight bearing with daily dosing on days 24 to 28.

Two-way repeated measure ANOVA with Dunnett's multiple comparisons post-hoc test