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

项目摘要/摘要 儿科慢性广泛性疼痛(CWP)是一个严重的公共卫生问题，导致高水平的医疗保健 使用率和伤残。患有煤工尘肺的青少年也经常报告接触过不良的童年经历 (A；滥用/疏忽等)而且有一个重要的子集继续经历长期的损害。一定要有思想- 身体干预，如基于正念的减压(MBSR)可能特别适合于 儿科CWP已被证明可调节应激诱导的HPA轴、自主神经的适应不良 神经系统和大脑结构(如海马体)。然而，目前尚不清楚这些目标是否 影响儿童煤工尘肺。初步研究表明，非平衡负荷(AL)，或“磨损”，对 神经系统由于应激，可能导致慢性疼痛。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，它在疼痛中扮演着重要角色 感知力。然而，到目前为止，还没有研究检查AL和海马体功能与压力的关系 暴露于儿童煤工尘肺。像MBSR这样的心身干预是一种重要且安全的治疗选择 对于儿童煤工尘肺的疼痛和压力的减轻，并可能调节ACE的负面影响，因此有 迫切需要知道这些机制是否参与了这一人群。建议的研究项目 利用多因素生理和神经成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。这样做的目的是 提交意见书是为了更好地表征AL，通过多因素组合评估，以及海马区功能 通过功能磁共振成像在儿童煤工尘肺中作为心身干预的特定目标，可以导致治疗的优化。 这个K23奖项的长期目标是让候选人建立一个独立的研究生涯，旨在 进行机械知晓的身心干预。CWP被选为模型条件是因为 它在儿科疼痛临床中的共性，以及与中枢敏化、高应激和 功能性残疾。培训的主要目标是获得神经生物学测量和 解释并利用目前的研究活动来补充这项提议，这将为 作为一名独立的研究人员，为机械驱动的临床试验拨款提交提供基础。这个 应聘者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 应激生理效应的神经生物学测量，辅以教学 神经内分泌和功能磁共振成像测量，3)先进数据分析技术的指导和课程工作， 4)利用心理社会实践活动和临床试验参与，同时努力 拟议奖励；以及5)执行拟议研究计划并提交一名独立调查员 获奖申请。这些活动将提供必要的数据，为R01临床的发展提供信息 本研究旨在检验青年煤工尘肺患者心身干预反应的生理机制(S)。

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.