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)

项目摘要： 联邦疼痛研究战略强调了研究生物学机制的必要性， 是儿科慢性疼痛患者非药物干预治疗效果的基础。 了解生物学机制可以促进有效治疗的使用，如认知疗法。 行为疗法（CBT）通过为患者和家庭提供更强的治疗理由， 减少耻辱感，增强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， 提供更加个性化和精确的护理，并将增加卫生保健提供者，患者， 和付款人。神经影像学和定量感觉测试（QST）是可以深入了解 疼痛治疗效果的生物学基础。该项目将研究偏头痛，影响超过600万青年， 美国科克伦综述表明，儿童头痛的心理治疗结果更好 与对照组相比（在714名参与者中，56%的人改善了，22%的人改善了），我们的CBT+阿米替林研究发现， 66%患有慢性偏头痛的年轻人头痛天数减少≥ 50%，相比之下， 对照组+AMI组。尽管有这样的证据基础， CBT对疼痛的疗效仍然知之甚少。缺乏机械的理解是一个障碍， 治疗利用率，特别是考虑到儿童偏头痛患者接受治疗的时间、精力和费用， CBT与常规药物治疗（在一项国家试验中， 安慰剂药丸：AMI 52%的参与者改善;安慰剂61%）。我们小组的试点数据表明： CBT诱导大脑连接/激活的变化，基线QST预测8岁时偏头痛减少 周这些发现证明了针对儿童偏头痛患者的概念，并改进了 该项目将招募240名年龄在10至17岁之间的偏头痛青少年， 以及在CBT、安慰剂或AMI治疗8周后，以解决这些目标：目标1：CBT是否参与大脑 机制，是不同于那些从事基于药丸的治疗（安慰剂和AMI）？目标2：更穷 通过QST测量的基线疼痛调节机制预测头痛天数从 CBT与基于药丸的治疗？探索目标：a.评估那些在第8周时大脑是否发生变化的人， 在3个月随访时评估结果时，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） 包括在统计模型中; c.比较安慰剂和AMI之间的神经影像学; d.所有分析将 包括年龄、性别、青春期状态和大脑结构连接， 发展变量儿科医学和行为临床医生可以使用来自 翻译研究，如这个项目，以加强他们提供的照顾青年偏头痛。

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.