Neurobiological Mechanisms of Stress in Youth with Chronic Widespread Pain - Supplement

患有慢性广泛疼痛的青少年压力的神经生物学机制 - 补充

• 批准号: 10604412
• 负责人: Sarah Mary Nelson
• 金额: $ 5.3万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10604412
• 关键词: Acute; Adult; Affect; Age; Anxiety; Area; Autonomic nervous system; Award; Blood Pressure; Body mass index; Boston; Brain; Cardiovascular system; Childhood; Clinical Research; Clinical Trials; Clinical Trials Design; Code; Community Hospitals; Complement; Data; Data Analytics; Development; Environment; Ethnic Origin; Evaluation; Exhibits; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Heart; Hippocampus (Brain); Home environment; Hydrocortisone; Impairment; Investigation; Lead; Measurement; Measures; Meditation; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentorship; Mind-Body Intervention; Modeling; Nervous system structure; Neurobiology; Neurologic Dysfunctions; Neurosecretory Systems; Outcome; Pain; Pain Clinics; Pain management; Parasympathetic Nervous System; Participant; Patients; Pediatric Hospitals; Physiological; Play; Population; Public Health; Race; Recording of previous events; Reporting; Research; Research Activity; Research Personnel; Research Project Grants; Research Training; Rest; Risk; Risk Factors; Role; Salivary; Schedule; Sleep; Stress; Structure; Sum; Techniques; Testing; Time; Training; United States National Institutes of Health; Violence; Waist-Hip Ratio; Well Child Visits; Work; Youth; abuse neglect; adverse childhood events; allostatic load; base; biological sex; career; central sensitization; chronic pain; chronic painful condition; chronic widespread pain; clinical pain; dehydroepiandrosterone; disability; experience; follow-up; functional disability; health care service utilization; hypothalamic-pituitary-adrenal axis; improved; lipid I; longitudinal design; mindfulness-based stress reduction; neurobiological mechanism; neuroimaging; novel; pain perception; pain reduction; primary outcome; programs; psychologic; psychosocial; public health relevance; recruit; research study; response; secondary outcome; sex; stress reduction; treatment optimization; treatment response; treatment services; wearable sensor technology

Project Summary/Abstract Pediatric chronic widespread pain (CWP) is a serious public health problem resulting in high levels of healthcare utilization and disability. Youth with CWP also frequently report exposure to adverse childhood experiences (ACEs; abuse/neglect, etc.) and a significant subset continue to experience impairment long-term. Certain mind- body interventions such as mindfulness-based stress reduction (MBSR) may be particularly appropriate for pediatric CWP as they have been shown to modulate stress-induced maladaptation of the HPA-axis, autonomic nervous system, and brain structure (e.g., hippocampus). However, it is currently unknown if these targets are affected in pediatric CWP. Preliminary research indicates that allostatic load (AL), or “wear and tear” on the nervous system due to stress, may contribute to pain chronicity. Similarly, evidence suggests that the hippocampus, a brain structure that is among the most deleteriously affected by stress, plays a role in pain perception. However, no study to-date has examined AL and hippocampal functioning in relation to stress exposure in pediatric CWP. Mind-body interventions such as MBSR are an important and safe therapy option for both pain and stress reduction in pediatric CWP and may modulate the negative impact of ACEs, so there is a critical need to know if these mechanisms are engaged in this population. The proposed research project utilizes multifactorial physiological and neuroimaging measurement techniques to enhance our understanding of the potential role of these mechanisms in impairment and mind-body intervention response. The aims of this submission are to better characterize AL, assessed via a multifactorial composite, and hippocampal functioning via fMRI in pediatric CWP as specific targets for mind-body interventions that can lead to treatment optimization. The long-term goal of this K23 award is for the candidate to establish an independent research career aimed at carrying out mechanistically informed mind-body interventions. CWP was selected as a model condition because of its commonality within pediatric pain clinics and strong association with central sensitization, high stress, and functional disability. The primary training objectives are to acquire expertise in neurobiological measurement and interpretation and to leverage current research activities complementary to this proposal that will lay the foundation for mechanistically driven clinical trial grant submissions as an independent investigator. The candidate will accomplish this through: 1) mentorship in a clinical/research environment, 2) hands-on training in the neurobiological measurement of the physiological effects of stress, complemented by didactics in neuroendocrine and fMRI measurement, 3) mentorship and coursework in advanced data analytic techniques, 4) leveraging psychosocial practice activities and clinical trial involvement in conjunction with effort on the proposed award, and 5) execution of the proposed research plan and submission of an independent investigator award application. These activities will provide the necessary data to inform the development of an R01 clinical trial designed to test the physiological mechanism(s) of mind-body intervention response in youth with CWP.

项目概要/摘要 小儿慢性广泛性疼痛 (CWP) 是一个严重的公共卫生问题，需要高水平的医疗保健 利用和残疾。患有 CWP 的青少年也经常报告有过不良的童年经历 （ACE；滥用/忽视等）和一个重要的子集继续长期遭受损害。一定的心思—— 身体干预措施，例如基于正念的减压（MBSR）可能特别适合 儿科 CWP，因为它们已被证明可以调节应激引起的 HPA 轴、自主神经适应不良 神经系统和大脑结构（例如海马体）。但目前尚不清楚这些目标是否 儿科 CWP 受到影响。初步研究表明，非稳态负载（AL），或“磨损” 神经系统由于压力，可能会导致疼痛的慢性化。同样，有证据表明 海马体是受压力影响最严重的大脑结构之一，在疼痛中发挥着重要作用 洞察力。然而，迄今为止还没有研究检查 AL 和海马功能与压力的关系 儿科 CWP 中的暴露。身心干预（例如 MBSR）是一种重要且安全的治疗选择 可以减轻儿科 CWP 的疼痛和压力，并且可以调节 ACE 的负面影响，因此 迫切需要知道这些机制是否在该人群中发挥作用。拟议的研究项目 利用多因素生理和神经影像测量技术来增强我们对 这些机制在损伤和身心干预反应中的潜在作用。本次活动的目的 提交的内容是为了更好地描述 AL 的特征，通过多因素综合评估和海马功能 通过儿科 CWP 中的功能磁共振成像作为身心干预的具体目标，可以优化治疗。 该 K23 奖项的长期目标是让候选人建立独立的研究生涯，旨在 进行机械知情的身心干预。选择 CWP 作为模型条件是因为 它在儿科疼痛诊所中的共性以及与中枢敏化、高压力和 功能障碍。主要培训目标是获得神经生物学测量和 解释并利用当前的研究活动补充该提案，这将奠定 作为独立研究者以机械方式驱动的临床试验拨款申请的基础。这 候选人将通过以下方式实现这一目标：1）临床/研究环境中的指导，2）实践培训 压力生理效应的神经生物学测量，并辅以教学法 神经内分泌和功能磁共振成像测量，3) 高级数据分析技术的指导和课程， 4) 结合社会心理实践活动和临床试验参与 拟议的奖励，以及 5) 执行拟议的研究计划并提交独立研究者的意见 奖励申请。这些活动将为 R01 临床开发提供必要的数据 旨在测试患有 CWP 的青少年身心干预反应的生理机制的试验。