Post-traumatic osteoarthritis in aged rodents is associated with brain changes that correlate with joint remodeling.

Abstract

Preclinical models of osteoarthritis (OA) can provide insights into joint-level remodeling and pain-related behaviors, but effects beyond the joint are poorly understood. The current study investigates joint remodeling and brain remodeling using aged rats in a surgical rodent model of post-traumatic OA. Male and female Fischer 344 rats (68 weeks old) received either a skin incision (n=6 male and n=10 female) or medial collateral ligament transection plus medial meniscus transection (MCLT+MMT) surgery (n=5 male and n=11 female). Tactile sensitivity was assessed pre-surgery and 4-, 8-, 12-, and 16-weeks post-surgery. Neuroimaging was performed pre-surgery and 6- and 14-weeks post-surgery, with analyses focused on gray matter volume, blood oxygen level dependent (BOLD) signal, and functional connectivity. Following euthanasia, histological analysis was performed to assess joint changes. Histology confirmed advanced cartilage loss and bone damage in animals with MCLT+MMT animals relative to skin-incision sham; however, tactile sensitivity decreased over time for both surgery groups. From the neuroimaging data, differences between the MCLT+MMT and skin-incision groups were present for both males and females at week 6 and week 14. Differences include gray matter volume, BOLD signal, and functional connectivity in regions responsible for pain transmission and modulation (thalamus, somatosensory cortex, and periaqueductal gray), along with the emotional and affective aspects of pain (striatum, hippocampus, prefrontal cortex, and amygdala). Despite a lack of differences in tactile sensitivity between groups, these findings in the central circuits involved in sensory and nociceptive processing indicate an association with knee OA development and brain remodeling. PERSPECTIVE: This work is the first to examine brain remodeling in the acute and chronic stages of osteoarthritis pain using the medial meniscus transection model in aged animals. Results demonstrate evidence of brain remodeling in a preclinical model of osteoarthritis and help elucidate osteoarthritis effects beyond the joint.