A Novel Rat Model of Ankle Osteoarthritis Induced by the Application of Monoiodoacetate

Abstract

Although ankle osteoarthritis is a common human joint disease, the etiological mechanisms underlying the associated pain remain unknown. We developed a new rat model of ankle osteoarthritis (OA) induced by monoiodoacetate (MIA) and evaluated the behavioral and histological characteristics of these animals. 60 male Sprague-Dawley rats were divided into three experimental groups of 20 rats. OA was induced by injecting the metabolic inhibitor MIA (1 mg/30 μl) into the tibiotarsal joint of the right hind paw on two consecutive days (MIA2 group) or single day (MIA1 group). Saline was injected into sham rats using the same protocol (sham group). We examined ankle swelling, range of motion, and stride length. We also assessed pain related behavior by observing the mechanical and thermal withdrawal responses. Rats were sacrificed 28 days after MIA/saline injection, and the right ankle joints were removed. Ankle sections were stained with safranin-O fast green, and histopathological changes were observed and scored. Both MIA groups exhibited significant increase in the ankle anteroposterior and transverse diameters (i.e., swelling) on days 7, 14, 21, and 28 post-injection relative to sham, as well as significantly decrease ROMs of the ankle. MIA2 rats additionally had a significantly shorter stride than did sham rats. MIA2 rats also exhibited an increased mechanical response frequency to the von Frey hair 4 g, and 6g tests, compared with sham rats, whereas MIA1 rats did not differ significantly from sham rats. Both MIA2 and MIA1 rats exhibited significantly reduced thermal latency in the hind paw relative to the sham group on day 28 post-injection. Histologically, the both MIA groups had a significantly higher score on day 28 post-injection, compared with the sham rats. MIA2 rats also exhibited more histological evidence of cartilage damage and abnormal medial tibia morphology, compared to MIA1 and sham rats.