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Chronic pain is a hallmark of joint diseases and a significant number of people with arthritis experience severe persistent pain that is not adequately managed with current treatments. Importantly, patients with joint pain often experience symptoms such as low mood, anxiety, overwhelming tiredness and lack of energy (also called fatigue) as well as memory dysfunction, conditions that altogether significantly impact patients’ well-being. While the sensory aspects of joint diseases have been extensively studied in animal models, associated mood-related disorders are rarely assessed in basic research. The efficacy of pain-relieving therapies in improving mood-disorders is also seldom investigated. Here, I will discuss data from pre-clinical work where we have used a battery of behavioural tests in mice with joint pain (1) to assess affective- and sleep-related disorders that often affect people with arthritis and (2) to investigate the efficacy of a novel treatment, the inhibition of the stress regulator FKBP51, designed not only to reduce persistent pain but also to directly improve mood-related disorders.