Pain Mechanisms in Rheumatoid Arthritis: Overlap and Distinguishing Characteristics Compared to other Chronic Pain Conditions

Musculoskeletal pain is the leading cause of disability in the world, and the number one reason patients with arthritis visit healthcare providers. Safe and effective, non-opioid analgesics are lacking, and over half of patients with inflammatory arthritis report pain, despite treatment with strong immunomodulatory drugs. Our research team was one of the first to show that patients with rheumatoid arthritis (RA) have impairments in pain processing, consistent with CNS pain sensitization, otherwise termed nociplastic pain. Once established, nociplastic pain often occurs in the absence of detectable peripheral inflammation. Inflammation may, however, serve as a trigger for developing nociplastic pain and/or be a factor in maintaining nociplastic pain. In animal models, an acute episode of inflammation can prime the hyperalgesic response to a second stimulus, resulting in long-lasting hyperalgesia. In humans, there is an increased prevalence of fibromyalgia (FM), the prototypical nociplastic pain condition, among patients with chronic inflammatory diseases, including RA, endometriosis, and inflammatory bowel disease. Little is known, however, about the cellular, physiologic, and biopsychosocial pathways that drive the transition from acute peripheral/visceral pain to chronic nociplastic pain in these diseases. In this presentation, we will review existing literature and discuss challenges and opportunities for future interdisciplinary research.