Sleep and circadian rhythm disturbances as risk and progression factors for multiple chronic pain conditions

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PROJECT SUMMARY Chronic pain affects more than one third of the U.S. population, incurring an annual health care cost of $1 trillion. Some of the most prevalent “idiopathic” pain conditions that frequently co-occur, such as chronic low back pain (cLBP), temporomandibular disorders, and fibromyalgia, are referred to as Chronic Overlapping Pain Conditions (COPCs). Among various COPCs, cLBP has the highest prevalence and is one of the top 10 most disabling conditions worldwide. Unfortunately, having multiple COPCs can further interfere with individuals' adaptive pain coping and exacerbate pain-related disability. However, much focus to date has been placed on individual anatomically-based chronic pain conditions and/or one COPC at a time, while little is known about the mechanisms underlying progression to multiple COPCs. A paradigm shift from anatomy-based approaches to mechanism-based approaches recognizing common and modifiable risk factors of multiple COPCs is crucial in developing effective interventions to treat and prevent multiple COPCs. Emerging evidence suggests that sleep and circadian rhythm disturbances—common clinical features across COPCs—that are modifiable, may serve an important role in progression to multiple COPCs via enhancement of pain amplification and psychological distress, which are two critical proximal determinants of multiple COPCs. For the present study, we propose to recruit a total of 300 participants with cLBP (i.e., 200 with cLBP only vs. 100 with cLBP and other COPCs) at baseline. Among these, 200 participants with cLBP only will be followed for 12 months. Sleep and circadian rhythms will be assessed longitudinally (i.e., baseline and 6-month follow-up) using a cutting- edge wireless EEG sleep monitoring device, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin (aMT6s), wrist worn actigraphy, and daily sleep diaries. Pain amplification (measured by quantitative sensory testing), psychological distress (measured by well-validated self-report measures), and the number of pain sites (measured by a well-validated pain body map) will be assessed at baseline, and 6- and 12-month follow- up visits. The proposed study will (1) comprehensively characterize the severity of sleep and circadian disturbances using ecologically valid multimodal ambulatory assessments among individuals with single and multiple COPCs; (2) prospectively examine whether baseline and changes (0 to 6 months) in sleep and circadian disturbances are associated with changes (0 to 6 months) in pain amplification and psychological distress; and (3) whether pain amplification and psychological distress at 6 months and their changes (6 to 12 months) are related to progression (6 to 12 months) in the number of pain sites (i.e., a valid proxy measure of multiple COPCs), while controlling for the effects of baseline sleep and circadian disturbances. The findings from this proposed work will provide novel insights into potential mechanistic pathways underlying progression to multiple COPCs, which may inform treatment and prevention strategies for these challenging conditions.