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

摘要 据估计，美国有6500万人患有腰痛，而美国黑人 不成比例地受到疼痛的有害后果的影响，包括更高的皈依率 与非西班牙裔白人相比，慢性疼痛、功能能力、情绪和生活质量下降 (卫生重量)。关于保守的逆境转录反应(CTRA)的经验证据表明 不利的心理社会状况，如由于经历过歧视或低落而感觉到的压力 社会经济地位，导致炎症和应激相关基因表达增加 小路。虽然从理论上讲，这些途径与影响从急性到 慢性疼痛，CTRA从未在有慢性疼痛风险的黑人个体中进行过系统的检查 慢性疼痛轨迹。此F31应用程序旨在为申请者提供知识和 建立与疼痛相关的健康差异的研究轨迹的技能。他已经获得了一位 高度投入和富有成效的导师团队，以完成他的培训目标和完成学习目标。 申请者的总体目标是：1)深入了解疼痛的方法和措施 研究；2)建立健康差距理论和测量方面的专业知识；3)获得基因组学知识和 利用下一代技术实施严格的实验室技术的原则；4)执行 测序流水线，多组数据的统计分析和解释；5)推进和整合 对急性低血压向慢性低血压转变的心理社会和神经生物学机制的认识 美国黑人的背部疼痛。 拟议的研究是对已完成的初始队列的二次分析 一项研究(R01NR013932；n=220)跟踪了急性下腰痛开始时的个体，并对他们进行了跟踪 每六周一次，持续六个月。申请者将随机选择40名黑人和40名NHW参与者(20名男性 以及20名女性，总共80名参与者)出现慢性下腰痛。保存完整 被引入PAX基因试管并立即在-80oC冷冻的血液样本将被处理 (基线急性腰痛和6个月/慢性腰痛)RNA和DNA甲基化(DNaM) 用于评估基因x环境交互作用的测序。这项研究的目的是：1)找出 心理社会(疼痛严重程度和干扰、情绪、感受到的压力、工作满意度)和神经生物学 (定量感觉测试)因素；以及，2)检查差异的mRNA表达和dNaM图谱 黑人和NHW参与者之间的急性腰痛发作和6个月的随访。种族x性别 还将进行比较。拟议的研究将为建立 申请者的研究计划，并将确定影响疼痛相关健康差异的独特因素 黑人个体在未来可能被用来开发有针对性的治疗，在种族和文化上- 量身定制的疼痛自我管理干预措施。

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.