Neural mechanisms underlying the pain of juvenile idiopathic arthritis

Pain is the most common symptom of juvenile idiopathic arthritis (JIA) and is arguably a more important factor in disability than the progression of the disease itself. Studies have highlighted the extent of this pain and its persistence in some young patients despite effective disease control. Understanding and effective management of pain in JIA is limited, and improved diagnosis and treatment would benefit from increased knowledge of the mechanisms underlying pain in childhood. This Review focuses upon the developmental neurobiology of pain, reviewing studies in animal models that increase clinical understanding and inform treatment of the painful manifestations of JIA. Pain processing in the juvenile nervous system differs from that in adults: nociceptive thresholds are lower and endogenous pain control systems are slow to mature. Furthermore, increasing evidence points to tissue injury in childhood having prolonged effects upon the developing pain system. Injury, inflammation and stress in early life can 'prime' peripheral nociceptors and central pain circuits, such that the pain associated with tissue inflammation is exacerbated in later life. A developmental, mechanism-based approach towards developing novel targets for the treatment of pain in JIA might therefore benefit the patient both as a child and as an adult if the disease recurs or persists.