Case Studies Cost Savings Health Care Delivery Public Health Practices Societal & Financial Cost of Illness Duke University Clinical & Translational Science Institute

Biopsychosocial Determinants of Pain in Sickle Cell Disease

"Ten Redefined" by Hertz Nazaire
“Ten Redefined” by Hertz Nazaire (1973-2021), a Haitian-American artist whose goal was to draw attention to the lived experience of Sickle Cell Disease

This case study was submitted by the Duke Clinical & Translational Science Institute, a CTSA at Duke University.

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Summary

Many people with sickle cell disease (SCD) frequently experience severe pain, and the contributing factors to that symptom have not been fully understood.

Principal Investigator Mitchell Knisely and other researchers led a study for people with SCD who were ≥15 years of age and lived in North Carolina.

The goals of this study were to:

  1. Examine different SCD-related pain phenotypes based on the occurrence of severe pain in the past 6-months, and
  2. Identify blood levels of inflammatory biomarkers connected with occurrence of severe SCD pain in people with SCD.

Blood samples were collected from people with SCD to generate biomarker data; the samples were also stored for future research.

74 individuals with SCD participated in the study, more than 65% of whom reported severe pain occurring sometimes or often.

When evaluating inflammatory plasma markers associated with the frequency of severe pain, the soluble endothelial leukocyte adhesion molecule 1 (sE-selectin) biomarker was significantly associated with the pain phenotype groups. Particularly, participants reporting severe pain occurring often or always had significantly higher plasma concentrations of sE-selectin compared to the other pain groups.

sE-selectin is a glycoprotein commonly used as a marker of systemic endothelial dysfunction. The processes of endothelial activation and resultant dysfunction are particularly pertinent in SCD; these mechanisms contribute to the multifactorial pathology of SCD and can lead to long-term complications such as blood vessel and organ damage.

Significance

This study identified a biomarker that is significantly associated with pain in people with sickle cell disease, offering a new exploratory direction for research.

SCD is characterized by abnormally shaped red blood cells that can clump and stick to blood vessel walls, affecting the flow of oxygen throughout the body. In the United States, SCD disproportionality affects Blacks and African Americans.

Mitchell Knisely, PhD, RN

Research Team

Mitchell Knisely, PhD, RN (primary contact);i Paula Tanabe, PhD;i,ii Julia Walker, PhD;i,iii Qing Yang, PhD;i Nirmish Shah, MD;i,iii,iv Sydney Sullivan, MPHv

Duke University School of Nursing
iiDuke University School of Medicine
iiiDuke University Department of Medicine
ivDuke University Department of Pediatrics
vDuke Clinical & Translational Science Institute

SCD is the most commonly inherited blood disorder in the US and affects 1 in 396 Black Americans. It is now understood that the pathophysiology of SCD is quite complex, including elements of inflammation and adhesion, all of which contribute to significant vascular and organ damage over time. While these disease processes cause significant medical complications, severe pain is among the most common and impactful symptoms experienced by individuals with SCD.

Other than opioids, there are few effective treatments to manage pain in this population. More than half (55%) of adults with SCD report pain on the majority of days in a 6-month period, with 29% reporting pain ≥95% of the days. However, there is a limited understanding of the mechanisms unique to the development of persistent SCD pain. Few studies have explored the relationships between inflammatory biomarkers (i.e., cytokines) and SCD pain.

A better understanding of the occurrence of severe pain, as well as biological contributors, can lead to improved assessment and management of pain in this population.

Benefits

Demonstrated benefits are those that have been observed and are verifiable. Potential benefits are those logically expected with moderate to high confidence.


This study reported the frequent occurrence of severe pain and provided preliminary evidence of the potential role of endothelial dysfunction in chronic severe pain in this population. Demonstrated.

TSBM Community Domain

Identify potential biomarkers in the blood (i.e. sE-selectin) that may be associated with experiences of severe pain in patients with SCD. Identifying SCD-related biomarkers may help clinicians better understand which SCD patients are likely to experience extreme pain, and may help clinicians and patients better manage their pain. Demonstrated.

TSBM Community Domain

Reduce lifetime costs associated with SCD. Pain is the number one reason people with SCD seek emergency department care and are admitted to the hospital, ultimately contributing to the significant healthcare costs for this population. If we have more effective treatments and management of pain, there is potential for decreased health care encounters and cost savings. Potential.


Societal costs of SCD, such as lost work productivity, could be reduced with improved management of pain for this population. Potential.


This research has community and economic implications. The framework for these implications was derived from the Translational Science Benefits Model created by the Institute of Clinical & Translational Sciences at Washington University in St. Louis.

Community: This study reported the frequent occurrence of severe pain and provided preliminary evidence of the potential role of endothelial dysfunction in chronic severe pain in this population.

The study also identified potential biomarkers in the blood (i.e. sE-selectin) that may be associated with experiences of severe pain in patients with SCD. Identifying SCD-related biomarkers may help clinicians better understand which SCD patients are likely to experience extreme pain, and may help clinicians and patients better manage their pain.

If we can better understand and properly manage pain, we can improve quality of life and properly address health care needs.

Economic: The findings of this study have the potential to reduce lifetime costs associated with SCD. Pain is the number one reason people with SCD seek health care. If we have more effective treatments/management of pain, there is potential there will be decreased health care encounters and cost savings.

Health Equity Implications

Patients with SCD are often disenfranchised and underrepresented in clinical research. This pilot adds to the work aimed at improving outcomes in this population.

Health care professionals and medical institutions may stigmatize persons with SCD due to sociodemographic factors. Future research should create targeted interventions for providers to reduce the stigmatization of SCD patients, so that they receive equitable pain management and health care.

Comprehensive health care is essential to improving the well-being and quality of life of this underserved population.

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