Studying Intra-Individual Pain Variability in Sickle Cell Disease and Resolution of Pain after Hematopoietic Cell Transplant: A Novel Model System to Elucidate Mechanisms of Transition to Chronic Pain

项目摘要镰刀细胞病(SCD)在美国影响着100,000多人，主要来自 少数民族，导致严重的发病率和较差的生活质量，往往是由于反复发作和慢性 疼痛。SCD从复发性急性疼痛向慢性疼痛过渡的时间进程和机制 代表该领域的关键知识差距。更好地了解糖尿病的风险因素和发病机制 过渡到慢性疼痛可以促进有针对性和有效的干预措施的发展。候选人 和她的导师已经开发并建立了基于网络的电子疼痛日记的内容有效性 在病人的自然环境中捕捉瞬间的疼痛。这些方法也使这项研究 疼痛强度的波动或个体内部差异，与疼痛强度不同，作为疼痛强度的重要方面 SCD的疼痛体验。现在可以应用这些方法来确定导致 慢性疼痛的发展是SCD患者的原因，以及找出导致慢性疼痛持续的因素 SCD经造血细胞移植(HCT)治愈后仍有疼痛。HCT提供了一种独特的模型 慢性疼痛的研究，其中潜在的镰状和血管闭塞被HCT去除。在这个目标1中 提案中，候选人将使用NIH赞助的两个大型多中心HCT临床试验的框架 SCD旨在解决疼痛变异性与患者报告的生理、社会和心理结果(PRO)的相关性 情绪功能，以及识别疼痛的表型。在目标2中，她将使用先进的统计模型 和定量感觉测试，以确定在SCD治愈的情况下导致疼痛持续的因素 Hct，疼痛的轨迹和专业人士，并将确定其疼痛最有可能受益的患者 HCT。在目标3中，她将第一次确定前瞻性纵向研究的可行性。 慢性疼痛在SCD中的发展。通过这个职业发展奖，候选人还将获得 在高级统计方法方面的专业知识，在管理疼痛和专业终点方面的经验 在大型多中心试验中，以及在设计和执行前瞻性、纵向观察性研究中 SCD的慢性疼痛。应聘者是SCD唯一合格且有前途的早期临床研究员。 疼痛研究。她的咨询委员会由SCD专家组成(Lakshmanan Krishnamurti博士、Wally博士 SCD的HCT(Lakshmanan Krishnamurti博士和Edmund Waller博士)，以及 纵向日记数据建模的生物统计学方法(考特尼·麦克拉肯博士)Aflac癌症和 血液疾病中心和埃默里大学提供了一个出色的研究环境， 为候选人提供的资源和支持。研究和培训计划将允许应聘者建立 她是SCD、Pain和Pro研究的独特十字路口的独立临床研究员，以及 使用创新的方法在SCD慢性疼痛领域取得进展。

PROJECT SUMMARY Sickle Cell Disease (SCD) affects over 100,000 individuals in the U.S, mostly from minority ethnicities, leading to significant morbidity and poorer quality of life, often due to recurrent and chronic pain. The time course and mechanisms of transition from recurrent acute pain episodes to chronic pain in SCD represent critical knowledge gaps in the field. A better understanding of the risk factors and mechanisms of transition to chronic pain can facilitate the development of targeted and effective interventions. The candidate and her mentor have developed and established content validity of a web-based electronic pain diary which captures pain on a momentary level, in the patient’s natural environment. These methods also allow the study of fluctuations or intra-individual variability in pain intensity, distinct from pain intensity, as an important facet of the pain experience in SCD. These approaches can now be applied to identify the factors that contribute to the development of chronic pain is SCD patients, as well as to identify the factors that lead to persistence of chronic pain despite cure of SCD by hematopoietic cell transplantation (HCT). HCT provides a unique model for the study of chronic pain where the underlying sickling and vaso-occlusion are removed by HCT. In Aim 1 of this proposal, the candidate will use the framework of two large NIH-sponsored multi-center clinical trials of HCT for SCD to address the relevance of pain variability on patient-reported outcomes (PROs) of physical social and emotional functioning, and in identifying phenotypes of pain. In Aim 2, she will use advanced statistical models and quantitative sensory testing to identify the factors that contribute to pain persistence despite cure of SCD by HCT, the trajectories of pain and PROs, and will identify the patients whose pain is most likely to benefit from HCT. In Aim 3, she will, for the first time, determine the feasibility of a prospective, longitudinal study of the development of chronic pain in SCD. Through this career development award, the candidate will also acquire expertise in advanced statistical methods, gain experience in managing the collection of pain and PRO endpoints in large multicenter trials, and in the design and execution of prospective, longitudinal observational studies of chronic pain in SCD. The candidate is a uniquely qualified and promising early-career clinical investigator in SCD pain research. Her advisory committee consists of experts in SCD (Dr. Lakshmanan Krishnamurti, Dr. Wally Smith, and Dr. Clinton Joiner), HCT for SCD (Dr. Lakshmanan Krishnamurti, and Dr. Edmund Waller), and biostatistical methods for modeling longitudinal diary data (Dr. Courtney McCracken). The Aflac Cancer and Blood Disorders Center, and Emory University provide an outstanding research environment with requisite resources and support for the candidate. The research and training plan will allow the candidate to establish herself as an independent clinical investigator at the unique crossroads of SCD, pain and PRO research, and the use of innovative approaches to advance the field of chronic pain in SCD.