Skip to main content
Información en Español
National Center for Complementary and Integrative Health

Concept: NIH HEAL Initiative: Optimizing Therapies for Sickle Cell Disease Pain Management

Project Concept Review

Council Date: May 14, 2021

Program Director: Della White, Ph.D.

Background

The proposed concept will be part of the National Institutes of Health (NIH) HEAL (Helping to End Addiction Long-termSM) Initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL InitiativeSM seeks to bolster research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about HEAL is available at https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.  

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States, affecting up to 100,000 Americans, predominantly including individuals of African descent and those who self-identify as Black (i.e., 1 in 365 African American children is born with SCD) and individuals of Hispanic ethnicity (1 in 16,300 is born with SCD). The most common complication of SCD is pain. Severe acute pain episodes, primarily from vaso-occlusive crises, chronic persistent pain, and neuropathic pain, occur from childhood through adulthood. The debilitating nature of this combined pain burden contributes to high rates of hospitalizations, emergency room visits, and poor functional and psychosocial outcomes, and an increased rate of mortality.  

Pain management for individuals with SCD is complex and presents unique challenges that must be considered depending on the presenting pain type (e.g., acute pain episode vs. chronic pain). The management of acute SCD pain during a vaso-occlusive crisis and chronic SCD pain often includes opioid-based therapies, which do not always address other, co-occurring symptoms that may exacerbate pain, such as sleep disturbances, stress, anxiety, and depression. Further, evidence has demonstrated that while most patients who have received hematopoietic stem cell transplant (HSCT) as a curative therapy for SCD reduce or discontinue the use of opioids post-HSCT, approximately 40 percent of HSCT patients continue to have severe chronic pain. 

An additional challenge in addressing SCD pain is that the SCD population comprises racial and ethnic minorities who experience disparities in receiving quality comprehensive care for SCD. Disparities in SCD care have been linked to the stigma associated with this disease as well as social factors such as racism and socioeconomic status. Indeed, recent reports from the National Academies of Sciences, Engineering, and Medicine and the Pain Management Best Practices Inter-Agency Task Force described SCD as a health disparity condition and highlighted the need for a paradigm shift to provide comprehensive care delivery models for managing pain and improving the overall well-being and quality of life of individuals with SCD-associated pain. To address these combined challenges, a biopsychosocial approach to pain management that includes a multimodal approach that addresses biological, psychological, and social influences on pain provides an opportunity to treat the whole person, improve overall health status, and possibly mitigate some of the factors leading to the stigma associated with SCD. 

While opioid therapy remains vital for the management of acute SCD pain, nonopioid pharmacologic and nonpharmacologic approaches for pain management have been deemed feasible and of interest to individuals with SCD. Additional research is needed with larger sample sizes and longer follow-up to enhance the evidence base regarding the effectiveness and implementation of these interventions to reduce different SCD pain types and improve related psychological and functional outcomes. Also, to design and deliver impactful interventions aimed at reducing stigma and improving pain outcomes, additional research is needed to determine effective implementation strategies to reduce stigma and address pain management health inequities.

Purpose of Proposed Initiative

This National Center for Complementary and Integrative Health–led HEAL initiative will have multiple components to address the HEAL research focus area of clinical research to enhance pain management. This proposed initiative would support research in two areas: (1) multisite clinical trials to test the efficacy and effectiveness of single- or multicomponent nonopioid pharmacologic and nonpharmacologic approaches for acute and chronic SCD pain management, and (2) multisite implementation research trials to inform the uptake of nonopioid pharmacologic and nonpharmacologic approaches for acute and chronic SCD pain management in health care systems that serve the SCD population. Outcomes of interest for these studies include reduced symptoms of chronic pain between crises, reduced number of hospitalizations and emergency room visits, and increased time between visits. Trials supported in this initiative would also address the impact of these approaches on related psychological and functional outcomes to support improved overall well-being and quality of life and address stigma, structural health care system, and social factors that may hinder quality comprehensive care. This initiative seeks to leverage the existing HEAL Pain Management Effectiveness Research Network (ERN) and Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) program infrastructures to support additional studies on SCD pain management among pediatric, emerging adult, and adult populations.

Objectives

The objectives to be met by this initiative include but are not limited to the following:

  • Studies that provide options for the addition of nonopioid pharmacologic and nonpharmacologic approaches for pain management that may reduce use of opioids.
  • Studies that examine pain management as well as impact on comorbidities such as sleep disturbance, anxiety, and stress.
  • Studies that support interventions to address social and structural barriers, such as stigma and racial bias, to SCD pain management care.
  • Embedded pragmatic trials or implementation studies to evaluate the impact of health care system changes to improve adherence to evidence-based nonopioid pharmacologic and nonpharmacologic approaches for acute and chronic SCD pain management.