Brain mapping inflammatory-arthritis-related fatigue in the pursuit of novel therapeutics

Despite developments in pharmacological treatments, chronic fatigue is an unresolved issue for most people with inflammatory arthritis that severely disrupts their personal and working lives. Fatigue in these patients is not strongly linked with peripheral disease activity but is associated with CNS-derived symptoms such as chronic pain, sleep disturbance, and depression. Therefore, a neurobiological basis should be considered when pursuing novel fatigue-specific therapeutics. In this Review, we focus on clinical imaging biomarkers that map candidate brain regions and are crucial in fatigue pathophysiology. We then evaluate neuromodulation techniques that could affect these candidate brain regions and are potential treatment strategies for fatigue in patients with inflammatory arthritis. We delineate work that is still required for neuroimaging and neuromodulation to eventually become part of a clinical pathway to treat and manage fatigue.