Severe, disabling pain is the hallmark of sickle cell disease (SCD). SCD pain is associated with poor quality of life, early mortality, and high healthcare costs. Clinicians face great challenges in managing SCD pain because of the poor understanding of the etiology of chronic/persistent SCD pain and the absence of validated clinical prognostic tools that can accurately identify individuals with SCD who are at risk of developing severe, persistent pain with associated physical and/or psychological disability. The overall objective of this project is to identify predictors of pain severity and pain-related outcomes in SCD using a prospective, longitudinal study design informed by the biopsychosocial model of pain. This proposal is supported by the hypothesis that painspecific psychological and sensory factors are strong, modifiable predictors of SCD pain severity and painrelated outcomes. The understanding of pain-specific psychological and sensory predictors of SCD pain outcomes is anticipated to have important implications for (1) identifying SCD patients who are at risk for severe pain outcomes, (2) informing preventive and therapeutic management of SCD pain, and (3) selecting patients for clinical trials of non-opioid interventions for SCD pain. The hypothesis will be tested by pursuing two specific aims: Aim 1) Determine psychological predictors of pain outcomes; and Aim 2) Ascertain the strength of pain distribution and sensitivity as predictors of pain outcomes. The candidate will use reliable and well validated pain-specific patient-reported outcome (PRO) questionnaires to evaluate the strength of psychological factors for predicting pain severity and other pain-related outcomes in the study cohort (Aim 1) and will use body mapping and quantitative sensory testing (QST) to examine sensory predictors of pain outcomes (Aim 2). The prospective, longitudinal design of this study and the use of biopsychosocial model of pain are innovative. The candidate's long-term goal is to become an interdisciplinary SCD pain expert who is a leading contributor to the treatment and understanding of the etiology and prognosis of chronic pain in adolescents and young adults with SCD. Her interdisciplinary training background in pediatrics and anesthesiology uniquely positions her for pursuing this research agenda. Through a detailed and specific career development plan developed in conjunction with her mentoring panel, the candidate will acquire formal training and expertise in SCD management, QST, assessment of the conceptual and psychometric properties of PROs, and advanced statistical modeling (risk prediction and prognostic modeling). Her mentoring and advisory committee includes an outstanding group of experts in psychosocial influencers of chronic pain (Francis J. Keefe PhD, Duke), QST (Claudia M. Campbell PhD, Johns Hopkins), SCD (Nirmish Shah MD and Paula Tanabe PhD, Duke; and Wally Smith MD, Virginia Commonwealth University), predictive modeling (Yi-Ju Li, PhD, Duke) and prognostic research in pain (Andrey Bortsov MD/PhD, Duke). Successful completion of this project is anticipated to improve the quality of life of individuals living with SCD.

Sickle cell disease is a painful inherited disorder that affects approximately 100,000 people in the United States, and more than half of these individuals develop chronic or persistent pain that is often severe and disabling. The factors that predict whether an individual with sickle cell disease will develop severe, disabling pain are unclear. The goal of this project is to identify the factors that predict severe pain outcomes in these patients in order to improve pain management strategies and guide future studies of non-opioid therapies for treatment of their pain.