Mechanisms Underlying the Contribution of Sleep Disturbances to Chronic Pain (R21/R01, Clinical Trial Optional)

Council Date: FY2018 in the form of Program Announcement (PA) 

Program Director: Wen G. Chen, Ph.D. (NCCIH); (collaborative institutes and centers – NIDA and potentially others)    

Background 

Chronic pain impacts over one-third of the U.S. population, consumes substantial health care, and significantly reduces work productivity. Long-term management of chronic pain has largely relied on opioid-based pharmacologic interventions, which not only lacks long-term efficacy but also carries risks for adverse events, especially contributing to the national epidemic of opioid abuse and crisis. Hence, successful management of chronic pain requires a better understanding of the factors that contribute to the development of chronic pain as well as the development or identifications of new management strategies. 

Chronic sleep disorders are commonly co-occurring in patients with chronic pain. There is not only substantial evidence that chronic pain states can disrupt sleep, but also a growing literature base to support a directional association of sleep disturbance contributing to chronic pain and the potential of sleep treatments to reduce pain. For instance, there is evidence supporting that sleep disturbance may increase acute pain sensitivity, and that, conversely, increased sleep time can reduce acute pain sensitivity. In addition, emerging evidence indicates that sleep disturbances may also predict the development of chronic pain. Furthermore, a meta-analysis of a small collection of pilot nonpharmacologic treatments of insomnia among chronic pain populations reported a small overall effect of reduced pain for treatment vs. control groups. Although more work is needed to validate these clinical findings, the mechanisms by which sleep may impact pain and whether modulation of sleep mechanisms may influence the development and management of pain remain largely unclear.  

In 2014, NCCIH led a trans-National Institues of Health (NIH) workshop on “Contribution of Sleep Disturbances to Chronic Pain.”  In 2016, NCCIH, the National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research, and National Institute of Arthritis and Musculoskeletal and Skin Diseases issued a funding opportunity announcement (FOA) for “Administrative Supplements for Research on Sleep Disturbances and Impact on Chronic Pain.”  

Purpose of Proposed Initiative

The purpose of this set of FOAs is to encourage mechanistic research to investigate the impact of sleep disturbances to chronic pain. The mechanisms and processes that underlie the contribution of sleep disturbances to chronic pain may be very broad. This FOA encourages interdisciplinary collaborations by experts from multiple fields—neuroscientists, psychologists, endocrinologists, immunologists, geneticists, pharmacologists, chemists, physicists, behavioral scientists, clinicians, caregivers, and others in relevant fields of inquiry. 

Objectives

Topics of interest include, but are not limited, to the following:

• The mechanisms by which nociception may be impacted by changes in sleep
• The mechanisms by which hypothalamic neurons or other mechanisms involved in sleep regulation may affect nociceptive pathways
• The mechanisms by which central pain-modulatory processes may be impacted by deficient sleep or circadian dysregulation
• Neural/glial mechanisms underlying the effect of sleep on the transition from acute to chronic pain
• The mechanisms by which pharmacologic interventions of sleep may impact chronic pain 
• The mechanisms by which nonpharmacologic or complementary and integrative health approaches of sleep regulation may impact chronic pain 
• The mechanisms by which complementary therapies, medications, and potential substances of abuse (e.g. nicotine, alcohol, caffeine) interact with sleep to increase or mitigate pain.

The FOAs support studying in appropriate model organisms or human subjects. This FOA may support clinical trials in which the primary outcomes are mechanistic. However, it should not be used for clinical trials in which the primary outcomes are clinical endpoints (e.g., clinical pain assessments), although clinical endpoints may be measured as secondary outcomes. Applications submitted should not include any specific aims that propose to measure efficacy or effectiveness of any intervention. Investigators who wish to conduct studies with clinical endpoints as the primary outcomes should consider other NIH-issued FOAs specifically designed for efficacy or effectiveness studies.