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)

项目总结： 联邦疼痛研究战略强调了对生物机制进行调查的必要性 非药物干预对儿科慢性疼痛患者的治疗效果。 了解生物学机制可以促进有效治疗方法的使用，如认知 行为疗法(CBT)通过为患者和家属提供更有力的治疗理由，从而 减少耻辱，增加对护理计划的信心和承诺。此外，机械制造 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准的护理，并将增加卫生保健提供者、患者、 和付款人。神经成像和定量感觉测试(QST)是一种可以提供对 疼痛治疗效果的生物学基础。这个项目将研究偏头痛，它影响着英国的600万青年。 美国的Cochrane评论表明，心理疗法对儿童头痛产生更好的结果 在714名参与者中，改善了56%，而在714名参与者中，改善了22%。我们的CBT+阿米替林研究发现 66%的患有慢性偏头痛的青年患者的头痛天数≥减少了50%，相比之下，患有慢性偏头痛的青年患者的 教育对照组+阿米替林(AMI)组。尽管有这样的证据基础，神经机制支持 CBT对疼痛的疗效仍然知之甚少。缺乏机械性的理解是一个障碍 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与传统药物疗法(在一项全国性试验中，该疗法减少头痛天数类似于 安慰剂：急性心肌梗死52%的参与者改善；安慰剂61%)。我们小组的试点数据表明： CBT导致大脑连接/激活的变化，基线的QST预测偏头痛在8岁时减轻 几周。这些发现证明了特定于儿童偏头痛患者的概念，并改进了设计 该项目将招募240名10至17岁的偏头痛青年进行功能磁共振成像和QST检查 在CBT、安慰剂或急性心肌梗死治疗8周后，以解决这些目标：目标1：CBT是否与大脑接触 与以药物为基础的治疗(安慰剂和心肌梗死)不同的机制是什么？目标2：更穷 QST测量的基线疼痛调节机制预测头痛天数从 CBT与以药物为基础的治疗？探索性目标：a.评估那些在8周时大脑是否发生变化 接受CBT在3个月的随访中起到中介作用；b.测试是否 当其他疼痛背景变量(焦虑、抑郁、睡眠)满足以下条件时，AIMS 1和AIMS 2的发现得到支持 包括在统计模型中；c.比较安慰剂和急性心肌梗死之间的神经成像；d.所有分析将 在统计模型中包括年龄、性别、青春期状态和大脑结构连通性 发展变数。儿科医疗和行为临床医生可以使用来自 翻译调查，如这一项目，以加强他们为偏头痛青年提供的护理。

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.