Identifying Differential Psychosocial and Neurobiological Risk Factors of the Transition from Acute to Chronic Pain in Black and Non-­Hispanic White Adults

Abstract Low back pain affects an estimated 65 million individuals in the United States, and Black Americans are disproportionately affected by the detrimental consequences of pain, including a higher incidence of converting to chronic pain, reduced functional capacity, mood, and quality of life compared to Non-Hispanic whites

(NHWs). Empirical evidence regarding the Conserved Transcriptional Response to Adversity (CTRA) suggests that adverse psychosocial conditions, such as perceived stress due to experienced discrimination or low socioeconomic status, cause increased expression of genes involved in inflammation and stress-related

pathways. While these pathways theoretically overlap with those that influence the transition from acute to chronic pain, the CTRA has never been systematically examined in Black individuals who are at risk of a chronic pain trajectory. This F31 application was designed to provide the applicant with the knowledge and

skills to establish a research trajectory in pain-related health disparities. He has garnered the support of a highly engaged and productive mentorship team to fulfill his traineeship goals and accomplish the study aims. The applicant’s overall goals are to: 1) gain a deep understanding of the methods and measures used in pain

research; 2) build expertise in health disparities theory and measures; 3) acquire genomics knowledge and principles for carrying out rigorous laboratory techniques with next generation technologies; 4) perform the sequencing pipeline, statistical analysis and interpretation of multi-omic data; and, 5) advance and integrate

knowledge of the psychosocial and neurobiological mechanisms of the transition from acute to chronic low back pain in Black Americans. The proposed study is a secondary analysis of a completed inception cohort study (R01NR013932; n=220) that tracked individuals at the onset of acute low back pain and followed them

every six weeks for six months. The applicant will randomly select 40 Black and 40 NHW participants (20 men and 20 women each for a total of 80 participants) who developed chronic low back pain. Preserved whole blood samples that were drawn into PAXgene tubes and immediately frozen at -80oC will be processed

(baseline acute low back pain and at 6-months/chronic low back pain) for RNA and DNA-methylation (DNAm) sequencing to assess gene x environment interactions. The study aims are to: 1) Identify differences in psychosocial (pain severity and interference, mood, perceived stress, work satisfaction) and neurobiological

(quantitative sensory testing) factors; and, 2) Examine differential mRNA expression and DNAm profiles between Black and NHW participants with low back pain at acute onset and at 6-months follow-up. Race x sex comparisons will also be conducted. The proposed study will provide a first-step toward establishing the

applicant’s program of research, and will identify unique factors that influence pain-related health disparities in Black individuals that may be used in the future to develop targeted therapy and ethnically and culturally- tailored pain self-management interventions.