Distinct Mechanisms of Cognitive Behavioral Therapy Effects in Youth with Migraine: Insights from Neuroimaging and Quantitative Sensory Testing (The How and Why Youth with Headaches Get Better Study)

认知行为治疗对偏头痛青少年的影响的独特机制：来自神经影像学和定量感官测试的见解（头痛青少年如何以及为何得到更好的研究）

• 批准号: 10395448
• 负责人: Robert C Coghill
• 金额: $ 60.31万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395448
• 关键词: Address; Adolescent; Adult; Affect; Age; Amitriptyline; Amygdaloid structure; Anxiety; Behavioral; Biological; Brain; Caring; Child; Childhood; Chronic; Cognitive Therapy; Data; Development; Disease; Education; Family; Fostering; Functional Magnetic Resonance Imaging; Headache; Health Personnel; Healthcare; Intervention; Investigation; Learning; Magnetic Resonance Imaging; Measures; Medical; Meditation; Mental Depression; Migraine; Neuraxis; Outcome; Pain; Pain Research; Pain management; Participant; Patients; Pattern; Pharmaceutical Preparations; Pharmacology; Placebo Effect; Placebos; Play; Prefrontal Cortex; Prevention; Randomized; Rest; Role; Self Management; Sensory; Sleep; Statistical Models; Structure; Techniques; Testing; Time; Work; Youth; arterial spin labeling; barrier to care; base; chronic pain patient; conditioned pain modulation; design; disability; effective therapy; evidence base; follow-up; improved; insight; migraine treatment; neuroimaging; neuromechanism; pediatric patients; pill; predict responsiveness; predicting response; predictive test; psychologic; recruit; sex; shared decision making; social stigma; treatment effect; uptake

Project Summary: The Federal Pain Research Strategy highlights the need for investigation of biological mechanisms that underlie the treatment effects of non-pharmacological interventions in pediatric chronic pain patients. Understanding biological mechanisms can advance the use of effective treatments such as cognitive behavioral therapy (CBT) by providing patients and families with a stronger rationale for treatment, thereby decreasing stigma and increasing confidence in and commitment to the care plan. In addition, mechanstic insights foster patients' ability to effectively participate in shared decision-making and self-management, may provide for more individualized and precise care, and will increase uptake by health care providers, patients, and payors. Neuroimaging and quantitative sensory testing (QST) are techniques that can provide insight into the biological basis for pain treatment effects. This project will study migraine, which affects > 6 million youth in the U.S. Cochrane reviews show that psychological therapies for pediatric headache result in better outcomes than control conditions (56% improved vs. 22% in 714 participants), and our CBT+Amitriptyline Study found that 66% of youth with chronic migraine had a ≥ 50% reduction in headache days compared to 36% in an education control+Amitriptyline (AMI) group. Despite this evidence base, the neural mechanisms supporting the efficacy of CBT for pain remain poorly understood. The lack of mechanistic understanding is a barrier to treatment utilization, particularly given the time, effort, and expense for pediatric migraine patients to receive CBT vs. conventional pharmacological therapy (which in a national trial reduced headache days similar to placebo pill: AMI 52% of participants improved; Placebo 61%). Pilot data from our group demonstrate that: CBT induces changes in brain connectivity/activation, and QST at baseline predicts reduced migraines at 8 weeks. These findings show proof of concept specific to pediatric migraine patients and refined the design of this project, which will recruit 240 youth ages 10 to 17 with migraine to undergo functional MRI and QST before and after 8 weeks of either CBT, placebo, or AMI to address these aims: Aim 1: Does CBT engage brain mechanisms which are distinct from those engaged by pill-based therapy (placebo & AMI)? Aim 2: Are poorer baseline pain modulatory mechanisms measured by QST predictive of greater headache day reduction from CBT vs. pill-based therapy? Exploratory Aims: a. Assess whether brain changes at 8 weeks in those who receive CBT play a mediational role when outcomes are assessed at a 3 month follow-up; b. Test if the findings from Aims 1 and 2 are supported when other pain contextual variables (anxiety, depression, sleep) are included in the statistical models; c. Compare neuroimaging between placebo and AMI; d. All analyses will include age, sex, pubertal status, and brain structural connectivity in the statistical models to assess developmental variables. Pediatric medical and behavioral clinicians can use mechanistic insights from translational investigations such as this project to enhance the care they provide to youth with migraine.

项目概要： 联邦疼痛研究战略强调了研究生物机制的必要性 这是非药物干预对儿科慢性疼痛患者治疗效果的基础。 了解生物机制可以促进有效治疗的使用，例如认知治疗 行为疗法（CBT）为患者和家庭提供更有力的治疗理由，从而 减少耻辱并增加对护理计划的信心和承诺。此外，机械 洞察力培养患者有效参与共同决策和自我管理的能力，可能 提供更加个性化和精确的护理，并将提高医疗保健提供者、患者、 和付款人。神经影像学和定量感觉测试 (QST) 技术可以深入了解 疼痛治疗效果的生物学基础。该项目将研究影响超过 600 万青少年的偏头痛 美国 Cochrane 综述表明，心理疗法治疗小儿头痛可带来更好的结果 与对照条件相比（714 名参与者中改善了 56%，而 714 名参与者改善了 22%），我们的 CBT+阿米替林研究发现 66% 患有慢性偏头痛的青少年的头痛天数减少了 50% 以上，而患有慢性偏头痛的青少年中这一比例为 36% 教育对照组+阿米替林(AMI)组。尽管有这样的证据基础，支持神经机制 CBT 对疼痛的疗效仍知之甚少。缺乏机制理解是实现这一目标的障碍 治疗利用率，特别是考虑到儿科偏头痛患者接受治疗的时间、精力和费用 CBT 与传统药物治疗（在一项全国试验中减少头痛天数，类似于 安慰剂药丸：52% 的参与者的 AMI 得到改善；安慰剂 61%）。我们小组的试点数据表明： CBT 会引起大脑连接/激活的变化，基线 QST 预计 8 岁时偏头痛会减少 几周。这些发现证明了针对儿科偏头痛患者的概念证明，并改进了设计 该项目将招募 240 名 10 至 17 岁患有偏头痛的青少年，在治疗前接受功能性 MRI 和 QST 经过 8 周的 CBT、安慰剂或 AMI 治疗以实现以下目标： 目标 1：CBT 是否能调动大脑 与基于药物的治疗（安慰剂和 AMI）所采用的机制有何不同？目标2：变得更穷 通过 QST 测量的基线疼痛调节机制可预测头痛日数减少 CBT 与基于药物的治疗？探索性目标：评估 8 周时大脑是否发生变化 在 3 个月的随访评估结果时，接受 CBT 发挥中介作用； b.测试是否 当其他疼痛背景变量（焦虑、抑郁、睡眠）得到满足时，目标 1 和 2 的发现得到支持 包含在统计模型中； c.比较安慰剂和 AMI 之间的神经影像学结果； d.所有分析将 将年龄、性别、青春期状态和大脑结构连接纳入统计模型中以评估 发展变量。儿科医学和行为临床医生可以利用来自以下方面的机械见解： 像这个项目这样的转化调查旨在加强他们为偏头痛青少年提供的护理。