Dissecting Neural Mechanisms Supporting Mind and Body Approaches to Pain Reduction in Youth with Migraine

剖析支持青少年偏头痛减轻疼痛的身心方法的神经机制

• 批准号: 10370373
• 负责人: Robert C Coghill
• 金额: $ 73万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-05 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10370373
• 关键词: Address; Adolescent; Adult; Affect; Age; Amitriptyline; Amygdaloid structure; Arousal; Biofeedback; Brain; Brain region; Breathing; Categories; Child; Childhood; Clinical Trials; Cognitive Therapy; Data; Disease; Education; Functional Magnetic Resonance Imaging; Goals; Guided imagery; Headache; Health; Imagery; Intervention; Magnetic Resonance Imaging; Migraine; Mind-Body Intervention; Modality; Multicenter Trials; Muscle Tension; Muscle relaxation phase; Neurobiology; Nociception; Outcome; Pain; Pain Research; Pain management; Patients; Pattern; Performance; Pharmaceutical Preparations; Pharmacology; Phase; Placebos; Play; Prefrontal Cortex; Prevention; Preventive; Process; Recurrence; Regulation; Relaxation; Relaxation Techniques; Relaxation Therapy; Rest; Role; Sampling; Sensory; Strategic Planning; Testing; Time; Training; Work; Youth; affective neuroscience; arterial spin labeling; barrier to care; clinical practice; cognitive control; cognitive reappraisal; conditioned pain modulation; disability; evidence base; experience; falls; indexing; migraine treatment; neuromechanism; pain reduction; pediatric patients; psychologic; recruit; somatosensory; stressor; topiramate

Migraine affects over 6 million children and adolescents in the U.S. and leads to significant pain and disability. Cognitive behavioral therapy (CBT) effectively reduces the number of headache days in pediatric patients. CBT includes distinct components, including mind and body approaches (deep breathing, progressive muscle relaxation, imagery, biofeedback) and cognitive reappraisal training (CR). While the new strategic plan of the National Center for Complementary and Integrated Health highlights “Neurobiological Effects and Mechanisms” as a top scientific priority for non-pharmacological pain research, the brain mechanisms by which components of CBT work remain poorly delineated. To dissect the neural mechanisms engaged by CBT, we will conduct a mechanistic clinical trial to compare a sample of 80 youth (ages 10 to 17) with migraine who receive relaxation training (BART) to 80 who receive CR training. Functional MRI and quantitative sensory testing (QST) data will be obtained before and after intervention (an 8 week period) to address these aims: Aim 1A. Do BART and CR training differentially alter resting brain activation in a fashion related to headache reduction? Our pilot data indicate migraine patients have pro-nociceptive patterns of functional connectivity with the amygdala while CBT produces anti-nociceptive patterns of amygdalar functional connectivity. We hypothesize that BART will preferentially activate the ventromedial prefrontal cortex (vmPFC) while CR training will preferentially activate the dorsolateral prefrontal cortex (dlPFC) and other regions of cognitive control. To test this, arterial spin labeling (ASL) MRI will be used to compare pre vs. post training differences in steady state brain activation in BART and CR groups. Resting state BOLD fMRI will be used to determine if BART and CR training produce differential alterations of the functional connectivity of the vmPFC and dlPFC with the amygdala. Aim 1B. Does active performance of BART and CR differentially recruit activation of the vmPFC and dlPFC? Preliminary data from CBT were obtained during rest and may reflect tonically active consequences of therapy/headache reduction rather than the phasic mechanisms involved during active engagement of BART/CR strategies. To further determine if BART and CR involve distinct brain mechanisms, both ASL and BOLD MRI will be used to compare brain activation and amygdalar functional connectivity during active performance of each treatment vs. rest. Aim 2. Does the efficiency of pain modulation predict headache reduction following BART vs. CR? QST assessment of the efficiency of conditioned pain modulation (CPM) provides an index of the involvement of endogenous pain modulatory mechanisms in both pain conditions and pain treatments. Our preliminary work has shown that low efficiency of CPM is predictive of headache reduction following CBT. However, it remains unknown if BART vs. CR is more effective in the presence of disrupted endogenous pain modulation. Thus, pre-treatment CPM will be used to test the hypothesis that low efficiency of CPM will be differentially predictive of headache reductions following BART vs. CR.

偏头痛影响美国超过600万儿童和青少年，并导致严重的疼痛和残疾。 认知行为疗法（CBT）有效地减少了小儿患者的标头天数。 CBT包括不同的组成部分，包括思维和身体方法（深呼吸，进行性肌肉 放松，图像，生物反馈）和认知重新评估培训（CR）。而新的战略计划 国家互补和综合健康中心重点介绍“神经生物学效应和 机制”作为非药物疼痛研究的最高科学优先级，大脑机制 CBT工作的组成部分仍然很差。为了剖析CBT参与的神经机制，我们 将进行机械临床试验，以比较80名青年（10至17岁）的样本与偏头痛 接受CR培训的80人接受放松培训（BART）。功能性MRI和定量感觉 测试（QST）数据将在干预之前和之后（为期8周）来解决以下目的：目标 1a。在与头痛有关 减少？我们的试点数据表明，偏头痛患者具有功能连接性的促伤害感受模式 使用杏仁核，而CBT产生杏仁核功能连接性的抗伤害感受模式。我们 假设BART将优先激活CR训练时腹侧前额叶皮层（VMPFC） 将优先激活背外侧前额叶皮层（DLPFC）和其他认知对照区域。到 测试这一点，将使用动脉自旋标记（ASL）MRI比较稳定的训练差异 BART和CR组的状态大脑激活。静止状态BOLD FMRI将用于确定Bart和Bart和 CR训练会导致VMPFC和DLPFC的功能连通性的不同变化 杏仁核。目标1B。 Bart和CR的积极性能是否对VMPFC的招募激活有所不同 DLPFC？在休息期间获得了来自CBT的初步数据，并可能反映出通常的主动后果 减少治疗/头痛，而不是积极参与期间所涉及的阶段机制 BART/CR策略。为了进一步确定巴特和CR是否涉及不同的大脑机制，ASL和 BOLD MRI将用于比较主动过程中大脑激活和杏仁核功能连接 每种治疗与休息的表现。 AIM 2。疼痛调制的效率是否预测标题 BART与CR之后减少？ QST评估条件疼痛调节效率（CPM） 提供了在疼痛条件和 疼痛治疗。我们的初步工作表明，CPM的低效率可预测标题 CBT后减少。但是，在存在的情况下，Bart vs. Cr是否更有效仍然未知 内源性疼痛调节中断。这是，治疗前CPM将用于检验以下假设。 CPM的效率将在Bart vs. Cr之后差异预测降低标题。