Molecular Mechanisms of Sex-Related Differences in Arthritis and Associated Pain

Clinical conditions leading to chronic pain show important sex-related differences in the prevalence, severity, and degree of functional disability. Decades of epidemiological and clinical studies have demonstrated that women are more sensitive to pain than men. Arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA), is much more prevalent in females and accounts for the majority of pain arising from musculoskeletal conditions. It is therefore important to understand the mechanisms governing sex-dependent differences in chronic pain, including arthritis pain. However, research into the mechanisms underlying the sex-related differences in arthritis-induced pain is still in its infancy due to the bias in biomedical research performed largely in male subjects and animals. In this review, we discuss current advances in both clinical and preclinical research regarding sex-related differences in the development or severity of arthritis and associated pain. In addition, sex-related differences in biological and molecular mechanisms underlying the pathogenesis of arthritis pain, elucidated based on clinical and preclinical findings, are reviewed.