Inflammation and bone and cartilage destruction in the synovial joints of rheumatoid arthritis (RA) is attributed to significant morbidity. In the presence if this damage, the threshold for activation of peripheral nociceptive neurons is lowered, resulting in pain with movement. It is also known that peripheral inflammation caused by RA can induce neuroinflammation. This is significant, as several neurodegenerative diseases, including Parkinson’s disease (PD), are linked to increased neuroinflammation. Thus, RA could place patients at higher risk of PD.

Aim: To evaluate the development of peripheral and central inflammation, bone loss and mechanical allodynia in a mild murine model of CAIA.

Clinical paw scoring showed CAIA+10µg LPS mice exhibited significantly greater paw inflammation compared with control mice from day 5-10 (p<0.05). Mechanical allodynia measurements showed a significant decrease in withdrawal response in CAIA+10µg LPS mice when compared to control mice on days 4-8 (p<0.05). Micro-CT scans determined that paw volume was significantly greater (p<0.01), while bone volume was significantly lower (p=0.01), in the front paws of diseased mice compared to control at day 10. Immunohistochemical staining showed there was a significant increase in number of IBA-1 positive microglia in the substantia nigra pars compacta (SNpc), the brain area in which dopaminergic cells degenerate in PD, in CAIA+10µg LPS mice compared to control (p=0.012).

The low dose of 10µg LPS in the CAIA model induced disease with greater inflammation and bone loss in the front paws of mice. CAIA mice had decreased paw withdrawal response, suggesting a reduction in pain as assessed by von Frey pain scores. Increased microglia in the SNpc indicate an enhanced inflammatory response within this brain region, which may be a key initiating factor in the later loss of dopaminergic neurons, and could place individuals with RA at increased risk of PD.