Advancing a Holistic Understanding of Variability in Lived Experience with Sickle Cell Pain - PROJECT SUMMARY/ABSTRACT This funding opportunity from the NIH HEAL Initiative calls for an authentic precision health approach to understanding and addressing pain and pain experiences. Sickle cell disease (SCD) is a historic, global, classic Mendelian disease with extensive phenotype variability attributable to diverse modifiers of disease severity. The hallmark of SCD is pain, which is multifaceted and woefully undermanaged. Pain is also the primary cause of hospitalization in patients with SCD and is correlated with increased morbidity, mortality, and healthcare costs, contributing to health disparities. Despite considerable research on SCD pain, with many singular associations, the findings have been largely disparate and tenuous. No studies have systematically modeled the SCD disease process or SCD pain as networks of relationships across multiple levels of influence. To improve pain assessment and management for SCD patients, we need a better understanding of the acute to chronic pain spectrum, how pain experiences unfold over time, and how individuals are affected by their pain state. The goal of this project is to develop and validate novel computational and clinical tools for understanding and addressing differences in pain experience and response to pain treatment among people with SCD. To that end, we will utilize the Globin Research Network for Data and Discovery (GRNDaD), a multisite SCD registry, to conduct a prospective cohort study of 1250 individuals (≥15 years of age) living with SCD in the US. Across three timepoints during a 3-year period, we will obtain representative measurements of the pain experience as well as known and putative exacerbators and ameliorators of acute and chronic SCD pain within seven domains (biological, clinical, behavioral, psychological, environmental, sociocultural, and structural), including the required NIH HEAL Common Data Elements (CDEs) and comorbidities such as depression, asthma, and substance use/misuse. This project will have three Aims: Aim 1: Create a set of Baseline Pain Profiles (BPPs) for SCD; Aim 2: Construct Precision Pain Profiles (PPPs) and compare them with the BPPs; and Aim 3: Develop Precision Models and Mechanisms (PMMs) that integrate diverse data types and explain the PPPs. The scope and expected deliverables of this project are unprecedented. This will be one of the most comprehensive investigations of the individual and collective influences of proximal and distal factors on SCD outcomes. Through this whole person approach, the study will generate new knowledge about the intricacies of pain; produce innovative statistical and computational methods and tools for SCD research and clinical care; and catalyze the development of novel and effective prevention, intervention, and treatment strategies that could help bring an end to the national opioid health crisis. What we learn about mitigating and managing SCD pain and pain in general will be translatable to other diseases and conditions globally.
