Pediatric Persistent Post-surgical Pain: From Animals to Application

小儿术后持续疼痛：从动物到应用

• 批准号: 9341363
• 负责人: Christine Barrett Sieberg
• 金额: $ 12.97万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-05 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9341363
• 关键词: Acute; Acute Pain; Adolescent; Adult; Affect; Age; American; Animal Genetics; Animal Model; Animals; Anxiety; Area; Behavior Therapy; Biological; Biological Assay; Blood; Chad; Child; Childhood; Chronic stress; Clinical; Clinical Research; Cohort Studies; Complement; Complex; DNA; Data; Development; Disease; Dysplasia; Environment; Environmental Risk Factor; Epigenetic Process; Etiology; Female; Future; Genes; Genetic; Goals; Grant; Health; Hip region structure; Human; Human Genetics; Idiopathic scoliosis; Injury; Institutional Review Boards; Investigation; K-Series Research Career Programs; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentorship; Methods; Modeling; Moods; Mus; Operative Surgical Procedures; Orthopedics; Osteotomy; Outcome; Pain; Pain Clinics; Pain Threshold; Patients; Pediatric Surgical Procedures; Persistent pain; Phenotype; Population; Postoperative Pain; Psychological Factors; Psychophysiology; Public Health; Recording of previous events; Relative Risks; Reporting; Research; Research Project Grants; Risk; Role; Sensory; Spinal Fusion; Stress; Structure; Surgical Models; Surveys; Techniques; Time; Training; Translational Research; United States; Youth; animal pain; arm; base; career; chronic pain; cohort; coping; cost; data modeling; design; disability; economic impact; emotional distress; functional disability; genetic predictors; genetic risk factor; genome wide association study; health care service utilization; improved; innovation; male; nerve injury; neurodevelopment; new therapeutic target; pediatric patients; phenotypic data; pre-clinical; prevent; prospective; psychologic; psychosocial; public health relevance; response; retention rate; risk variant; role model; sex; spared nerve; statistics

Project Summary/Abstract Pediatric chronic pain is a serious public health problem resulting in high levels of healthcare utilization and disability. The physical and psychological consequences associated with chronic pain impact overall health and can predispose the development of adult chronic pain. Specifically, there has been an inadequate amount of research conducted on pediatric persistent postsurgical pain (PPP), which is urgently required given that over 5 million children undergo surgery each year and 25% of adults presenting to chronic pain clinics identify surgery as the antecedent. The proposed translational research project utilizes animal models, humans, genetics, and psychophysiological techniques to enhance our understanding of these mechanisms. The long- term goal of this K23 award is for the candidate to establish an independent translational research career aimed at developing mechanistically based behavioral interventions. The intent of the proposed project is to develop an animal model exploring how gene-environmental interactions, age, and biological sex contribute to pre- and post surgical pain thresholds, which will serve as a first step to functionally assaying genetic mechanisms we hope to discover in the gene association arm of our human studies. The human arm of this project is two-fold; examining the role of childhood stress and genetic pain risk on current pain and functioning in a large cohort of adult surgical patients, as well as continuing an IRB-approved study examining the sensory, psychosocial, and genetic predictors of PPP and related functional disability in pediatric patients with either idiopathic scoliosis undergoing spinal fusion surgery or developmental dysplasia of the hip undergoing hip osteotomy. This population was selected as a model condition because these are orthopedic conditions affecting children, the children are otherwise healthy, and both surgeries are quite invasive and complex with our research indicating that that a high proportion of these patients go onto to develop moderate to severe pain after surgery. The primary training objective is to acquire expertise in pain genetics, animal models, and translational research. The candidate will accomplish this through: 1) mentorship in a clinical/research environment, 2) hands-on training in animal models and genetics by the candidate's sponsor and co-sponsors complemented by didactics in genetics and advanced statistics, and 3) execution of the proposed research plan. These studies will provide the necessary data to inform the development of an R01 to focus on an epigenetic model to identify study genes, which markedly alter the risk profile for PPP and which will inform the development of new drug targets and behavioral interventions for those at greatest risk.

项目概要/摘要 小儿慢性疼痛是一个严重的公共卫生问题，导致医疗保健利用率高， 残疾。与慢性疼痛相关的身体和心理后果影响整体健康 并可能导致成人慢性疼痛的发展。具体来说，金额不足 对儿科持续性术后疼痛（PPP）进行的研究，鉴于以下情况，迫切需要进行这项研究 每年有超过 500 万儿童接受手术，25% 到慢性疼痛诊所就诊的成年人发现 以手术为前提。拟议的转化研究项目利用动物模型、人类、 遗传学和心理生理学技术来增强我们对这些机制的理解。长- K23 奖项的长期目标是让候选人建立独立的转化研究生涯 旨在开发基于机械的行为干预措施。拟议项目的目的是 开发一个动物模型，探索基因-环境相互作用、年龄和生物性别如何影响 手术前和手术后疼痛阈值，这将作为功能分析遗传的第一步 我们希望在人类研究的基因关联部分中发现机制。这人类的手臂 项目有两个方面；检查童年压力和遗传疼痛风险对当前疼痛和功能的作用 在一大群成年手术患者中进行研究，并继续进行一项 IRB 批准的研究，检查感觉， 患有以下任一疾病的儿科患者 PPP 和相关功能障碍的社会心理和遗传预测因素 接受脊柱融合手术的特发性脊柱侧凸或接受髋关节发育不良的髋关节 截骨术。该人群被选为模型条件，因为这些是骨科条件 影响儿童，但儿童在其他方面都很健康，而且这两种手术都具有相当的侵入性和复杂性 我们的研究表明，这些患者中很大一部分会出现中度至重度疼痛 手术后。主要培训目标是获得疼痛遗传学、动物模型和 转化研究。候选人将通过以下方式实现这一目标：1）临床/研究指导 环境，2）由候选人的赞助者和共同赞助者进行动物模型和遗传学的实践培训 辅以遗传学和高级统计学教学法，以及3）执行拟议的研究 计划。这些研究将为 R01 的开发提供必要的数据，以重点关注 用于识别研究基因的表观遗传模型，这些基因显着改变 PPP 的风险状况，并将提供信息 为高危人群开发新的药物靶点和行为干预措施。