Like most people with arthritis, you probably have symptoms that are better at some times of day than others. Rheumatoid arthritis (RA) is usually worse in the morning, for instance, whereas gout more frequently flares in the evening, and pain from fibromyalgia (like other conditions) is more intense after a poor night’s sleep. Researchers believe these variations in the timing and severity of arthritis symptoms may result from disruptions in circadian rhythms – the 24-hour cycles of biologic activity that regulate sleep, immune response and many other functions.
Cortisol: At the Heart of the Matter
Maurizio Cutolo, MD, a professor of rheumatology at the University of Genova in Italy and a leading chronobiology researcher, says levels of cytokines, such as tumor necrosis factor (TNF) and interleukin 6 (IL-6), which play major roles in inflammatory arthritis, rise during the night. Normally, there is a corresponding midnight-to-morning rise in cortisol – a powerful anti-inflammatory produced by the adrenal glands. But people with RA don’t produce enough cortisol to suppress nighttime inflammation, leading to morning pain and stiffness.
Because cytokine production follows a 24-hour daily cycle, increasing in the evening then falling to near zero by noon, Dr. Cutolo suggests that RA patients take modified-release corticosteroids at bedtime to help fight inflammation when it’s at its highest.
Similar disrupted circadian patterns seem to occur in gout. A 2014 study in Arthritis & Rheumatology found the risk of gout flares was 2.4 times higher at night and 1.3 times higher in the early evening than during the day. Lead study author Hyon Choi, MD, director of clinical epidemiology at Massachusetts General Hospital in Boston, says this may be due to a noon-to-midnight drop in cortisol levels, among other factors. If so, gout medications, like other arthritis drugs, may be more effective when taken at night.
What’s Sleep Got to Do With It?
In people with fibromyalgia, insomnia and other sleep problems interfere with normal patterns of waking and sleeping – and therefore circadian rhythms – leading to reduced cortisol production and increased morning pain, according to Stanford University researchers. In studies, treating sleep problems improved musculoskeletal pain in some, but not all, fibromyalgia patients.
In fact, sleep disorders are common in almost all rheumatic diseases (including osteoarthritis, scleroderma and lupus), and there is likely a self-perpetuating cycle in which pain disturbs sleep, leading, in turn, to increased inflammation and more pain. Experts suggest that treating both sleep problems and pain may improve arthritis symptoms and even the underlying disease process.