Surgical Rodent Model of Osteoarthritis Alters Joint Structure, Tactile Sensitivity, and the Brain

Osteoarthritis (OA) is a debilitating and painful joint disorder with a significant impact on patient’s lives. However, the effects of OA on pain-processing regions in the brain are poorly understood. To address this gap, the current study investigates joint remodeling, pain-related behavior, and brain remodeling in a surgical rodent model of post-traumatic osteoarthritis. Male and female Fischer-344 rats (18-19 months) received either a skin-incision (n=6 male, n=10 female) or medial meniscus transection plus medial collateral ligament transection (MMT+MCLT) (n=5 male, n=11 female) surgery. Tactile sensitivity testing was performed before surgery and 4-, 8-, 12-, and 16- weeks post-surgery. Resting-state fMRI was collected on a 11 T/40 cm horizontal magnet (Bruker) at baseline and 6- and 14- weeks post-surgery. At endpoint, histological analysis of the knee was performed. All datasets were analyzed using linear mixed-effects models. In MMT+MCLT animals, there was a trend of decreased 50% withdrawal threshold compared to skin-incision controls at 4-,8-,12-, and 16- weeks post-surgery. Changes in functional connectivity were observed between the MMT+MCLT and skin-incision animals at 6 weeks and 14 weeks post-surgery (p-values<0.05 and effect size(eta-squared)>0.15). These changes focused on regions involved in nociception, pain modulation, and the limbic system – including the amygdala, hippocampus, striatum, thalamus, and somatosensory cortex. For joint remodeling, MMT+MCLT animals exhibited cartilage loss and subchondral bone sclerosis – consistent with prior work in this model. This study is our first look at resting-state fMRI and indicates that circuits involved in pain-processing are likely altered with this model of post-traumatic OA. Funding: R01AR071431, R01AR071431-S2.