Reprint of “Residual pain in rheumatoid arthritis: Is it a real problem?”

Pain is a significant issue in rheumatoid arthritis (RA) and can have a negative impact on patients' quality of life. Despite optimal control of inflammatory disease, residual chronic pain remains a major unmet medical need in RA. Pain in RA can be secondary to inflammation but can also generate neuroendocrine responses that initiate neurogenic inflammation and enhance cytokine release, leading to persistent hyperalgesia. In addition to well-known cytokines such as TNFα and IL-6, other cytokines and the JAK-STAT pathway play a role in pain modulation and inflammation. The development of chronic pain in RA involves processes beyond inflammation or structural damage. Residual pain is often observed in patients even after achieving remission or low disease activity, suggesting the involvement of non-inflammatory and central sensitization mechanisms. Moreover, fibromyalgia syndrome (FMS) is prevalent in RA patients and may contribute to persistent pain. Factors such as depression, sleep disturbance, and pro-inflammatory cytokines may contribute to the development of fibromyalgia in RA. It is essential to identify and diagnose concomitant FMS in RA patients to better manage their symptoms. Further research is needed to unravel the complexities of pain in RA. Finally, recent studies have shown that JAK inhibitors effectively reduce residual pain in RA patients, suggesting pain-reducing effects independent of their anti-inflammatory properties. •Despite widespread use of biologics in RA leading to excellent disease control, many patients still report persistent pain.•Treating RA pain with a target approach is important, but it can lead to overinflating disease measures and overtreatment.•Differentiating central pain from peripheral inflammation is important, as US in symptomatic patients without clinical signs.•Patients with fibromyalgia may be difficult-to-treat due to persistent pain, even after inflammation has resolved.•IL-6 and JAK inhibitors can relieve persistent pain by targeting peripheral and central pain pathways.