NIH HEAL Initiative Workshop - Interface Between Sleep and Pain: Symptomatology, Pathobiology, and Treatment Response (Virtual)

This is a virtual scientific workshop focused on the intersection between sleep/circadian rhythms and chronic pain conditions. The overall goal of the workshop is to identify opportunities to integrate advances in sleep and circadian science with priorities in pain biology, prevention, and therapeutics. The workshop will facilitate discussion on the state of science in sleep and pain research and provide important information for NIH program and strategic planning. 

Sleep deficiency (e.g., short sleep duration, irregular timing, poor sleep quality) and sleep disorders (e.g., insomnia, sleep apnea, shift work sleep disorder) are frequently co-morbid in individuals with acute and chronic pain conditions (e.g., osteoarthritis, neuropathy, cancer, sickle cell disease, temporomandibular disorders, fibromyalgia). Evidence points to a bi-directional relationship where sleep deficiency exacerbates pain sensitivity, and pain triggers sleep disruption. Sleep and circadian disturbances are modifiable and there is an unmet need to identify potential therapeutic targets to mitigate pain pathobiology and improve pain management and treatment response. This initiative will support clinical intervention research aimed to determine whether improving co-morbid sleep disturbances is a potential strategy to enhance pain management and outcomes in individuals where sleep perturbations and pain are co-morbid.

This NIH HEAL Initiative workshop is sponsored by the National Heart, Lung, and Blood Institute, National Center for Complementary and Integrative Health, and National Institute of Neurological Disorders and Stroke of the National Institutes of Health.

Topics Covered

• Delineate neural and peripheral mechanisms/therapeutic targets linking sleep disturbance and chronic pain pathophysiology; 
• Discuss the significance of circadian rhythms in pain symptomatology and hyperalgesia; 
• Identify strategies to improve sleep and circadian rhythm disturbances in the context of chronic pain conditions; 
• Examine whether sleep and circadian interventions should be integrated into pain management strategies.

Day 1: 10:00 am – 4:45 pm EST

Welcome and opening remarks

• Walter J. Koroshetz, MD (NIH/NINDS, Director)
• Helene Langevin MD (NIH/NCCIH, Director)

Workshop overview (Co-Chairs)

• Michael T. Smith, PhD (Johns Hopkins University)
• Monika Haack, PhD (Harvard Medical School)

SESSION 1 - HEAL Program Overview

Purpose: Discuss goals and major scientific components of the NIH HEAL OUD and Pain programs. Identify opportunities for sleep and circadian science to contribute to HEAL priorities and scientific deliverables.

• Wilson M. Compton, MD, MPE (NIH/NIDA, Deputy Director)
  “HEAL Opioid Use Disorder (OUD) Program Overview”
• Michael L. Oshinsky, PhD (NIH/NINDS)
  “HEAL Pain Program Overview”
• Moderator: Sunila Nair, PhD (NIH/NIDA)
  Questions/Discussion

KEYNOTES - Sleep and Chronic Pain

Purpose: Discuss conceptual models of sleep and chronic pain interface, and opportunities for scientific synergy.

• Michael V. Vitiello, PhD (University of Washington)
  “The Complex Relationship Between Sleep and Chronic Pain”
• Roger B. Fillingim, PhD (University of Florida)
  “Emerging Themes in Chronic Pain Research and Their Relevance to Sleep”
• Moderator: Aaron D. Laposky, PhD (NIH/NHLBI/NCSDR)
  Questions/Discussion

SESSION 2 - Mechanisms Linking Circadian Rhythms, Hyperalgesia, and Chronic Pain

Purpose: Discuss importance of circadian rhythms in chronic pain symptomatology, pathobiology and management. What is the significance of circadian rhythms in mechanisms of pain? How to improve measurement of rhythms in pain cohort and trial studies? Identify circadian-based interventions to improve pain management and treatment outcomes.

• Randy J. Nelson, PhD (West Virginia University)
  “Disrupted Circadian Rhythms and Altered Responses to Pain Stimuli and Opiates”
• Helen J. Burgess, PhD (University of Michigan)
  “Morning Light Treatment for Chronic Pain”
• Chung Jung Mun, PhD (Arizona State University)
  “The 24-Hour Cycle of Pain: Circadian Rhythmicity of Pain Sensitivity in Humans and Its Implications”
• Moderator: Janet He, PhD (NIH/NINDS)
  Questions/Discussion

SESSION 3 - PANEL: Mechanisms Linking Sleep/Circadian Rhythms, Hyperalgesia and Chronic Pain Risk

Purpose: Advance understanding of mechanisms linking sleep and acute/chronic pain at multiple levels of pain processing. Identify mechanisms by which sleep disturbance exacerbates hyperalgesia and/or makes the management of chronic pain more difficult. Apply basic discovery to identify potential mechanistic targets to intervene on the self-perpetuating cycle of sleep disturbance and chronic pain. Discuss novel strategies to investigate mechanisms linking sleep and chronic pain.

• Chloe Alexandre, PhD (Johns Hopkins University)
  “Unraveling the Neurobiological Mechanisms at the Interface of Sleep and Pain”
• Giancarlo Vanini, MD (University of Michigan) 
  “Preoptic-PAG Pathway Linking Sleep Loss and Pain”
• Rachel K. Rowe, PhD (University of Colorado)
  “Inflammatory Pathways that Mediate the Bidirectional Relationship Between Sleep and Pain”
• Tiffany J. Braley, MD, MS (University of Michigan)
  “Intersections Between Sleep, Pain, and Cannabinoid Use: Knowledge Gaps and Future Directions”
• Lauren M. Hablitz, PhD (University of Rochester)
  “The Glymphatic System Times Sleep and Pain”
• Fiona C. Baker, PhD (SRI International)
  “Sleep Disturbance, Alcohol Use, and Chronic Pain”
• Jamie L. Rhudy, PhD (University of Oklahoma)
  “How Sleep May Contribute to Native American Pain Inequities”
• Tony Cunningham, PhD (Harvard Medical School)
  “Sleep Loss and Emotional Regulation in Chronic Pain Pathobiology”
• Moderator: Shailesh Kumar, PhD (NIH/NIAAA)
  Questions/Discussion

Take-home points (Co-Chairs)
Adjourn Day 1

Day 2: 10:00 am – 4:00 pm EST

Welcome and opening remarks

• Inna Belfer, MD, PhD (NIH/NCCIH)
• Janet He, PhD (NIH/NINDS)

KEYNOTES - Sleep and Pain Pharmacology

Purpose: Discuss current developments in sleep and pain pharmacotherapies and interactions between targets and efficacy across sleep and pain conditions. Do sleep medications interfere with and/or improve pain symptoms and management? Do pain medications interfere with and/or improve sleep? What are critical gaps and opportunities for research with respect to treating co-morbid sleep and pain conditions?

• Andrew D. Krystal, MD, MS (University of California San Diego)
  “Pharmacology to Improve Sleep in the Context of Chronic Pain”
• Clifford J. Woolf, MB, BCh, PhD (Harvard Medical School)
  “Advances and Limitations of Pharmacology of Pain Management”
• Moderator: Aaron D. Laposky, PhD (NIH/NHLBI/NCSDR)
  Questions/Discussion

SESSION 4 - Cross-Cutting Priorities: Sex Differences and Disparities

Purpose: Discuss cross-cutting factors to consider across all basic and clinical research in sleep and pain. Research has identified sex and health disparities as centrally important in the etiology, pathobiology and management of sleep and pain conditions. Examine the importance of sex and disparities to the intersection of sleep and chronic pain.

• Sara Nowakowski, PhD, CBSM, DBSM (Baylor College of Medicine)
  “Sleep in Women Across the Lifespan in Relation to Pain Disorders”
• Jeffrey S. Mogil, PhD, FCAHS, FRSC (McGill University)
  “Pain, Sex, and Death”
• Carmen Renée Green, MD (City University of New York)
  “Disparities and Social Determinants in Chronic Pain”
• Chandra L. Jackson, PhD, MS (NIH/NIEHS)
  “Disparities in Sleep Health: Implications for Sleep-Pain Research”
• Moderator: Arielle Gillman, PhD, MPH (NIH/NIMHD)
  Questions/Discussion

SESSION 5 - Panel: Sleep and Circadian Interventions in Chronic Pain

Purpose: Discuss novel strategies to improve sleep in the context of chronic pain. Determine if improvements in sleep facilitate chronic pain management (i.e., person-centered and clinical outcomes). Does improving sleep result in better pain prevention, management and treatment? Do pain medications facilitate or impair sleep? Do sleep medications affect pain processing and symptoms? Do sleep problems vary by the type of pain condition? Is sleep adequately addressed in the assessment/treatment of chronic pain? If not, what is the barrier (e.g., education, lack of multi-disciplinary teams, lack of evidence that sleep will make a difference)?

• Kristin L. Schreiber, MD, PhD (Harvard Medical School)
  “The Perioperative Period as a Workshop for Understanding the Sleep-Pain Relationship and Testing Preventive Interventions”
• Fadel Zeidan, PhD (University of California San Diego)
  “Neural Mechanisms Supporting the Modulation of Chronic Pain by Mindfulness Meditation as Compared to Placebo”
• Patrick H. Finan, PhD (University of Virginia)
  “The Intersection of Sleep, Reward, and Pain: Pathways to Addiction Vulnerability”
• Tonja M. Palermo, PhD (Seattle Children’s Hospital)
  “Sleep, Chronotype, and Pain in Adolescents: Implications for Targeted Interventions”
• Cornelius B. Groenewald, MD (Stanford University)
  “Sleep and Acute Postoperative Pain in Adolescents”
• Gilles Lavigne, DMD, PhD, FRCD (McGill University)
  “Sleep Apnea and Orofacial Pain”
• Daniel Whibley, PhD (University of Michigan)
  “Combining Sleep Improvement and Physical Activity for Pain Management”
• Michael R. Irwin, MD (University of California Los Angeles)
  “Insomnia and Inflammation: Pathways to Depression”
• Moderator: Inna Belfer, MD, PhD (NIH/NCCIH)
  Questions/Discussion
  Closing Remarks

Take-home points (Co-Chairs)
Adjourn Workshop

For More Information, Contact:

Rhonise N. Simpson [email protected] (NHLBI)

Aaron D. Laposky, Ph.D., at [email protected] or 301-827-7837 (NHLBI)
Inna Belfer, MD, Ph.D., at [email protected] or 301-435-1573 (NCCIH)
Yejun (Janet) He, at [email protected] or 301-496-9964 (NINDS)