Mind and Body Approaches to Pain Reduction in Youth With Migraine

The overarching objective of this protocol is to identify and understand the neural and pain processing mechanisms by which youth with migraine improve in response to preventive treatment. The study design of this mechanistic investigation includes functional magnetic resonance imaging (fMRI), daily headache diaries, assessment of conditioned pain modulation via quantitative sensory testing, and validated psychometric assessments before and after the delivery of one of five treatments over an 8 week period \[cognitive behavioral therapy (CBT), biofeedback-assisted relaxation training (BART) and cognitive reappraisal (CR) training, amitriptyline, and placebo\]. We are examining both distinct and common pathways that may help explain the response to various preventive treatments, as well as potential predictors of outcome.

Pediatric migraine is a prevalent disorder that results in significant pain and disability for children and adolescents. Despite the prevalence and cost, commonly used pharmacologic treatments to treat pediatric migraine have limited evidence of efficacy over placebo in preventing migraine in youth. In our prior research, published in NEJM (Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. N Engl J Med. 2017;376(2):115-124),we have shown in a large, national, multicenter trial that the most widely used conventional preventive medications, amitriptyline (AMI) and topiramate, are no more effective than placebo. Psychological therapies for pediatric headache (in particular, cognitive behavioral therapy \[CBT\]) result in better outcomes than control conditions by effectively reducing headache days and disability in children and adolescents with migraine. Our own work indicates that youth receiving combined CBT plus amitriptyline (AMI, the most widely used migraine prophylactic in youth) had greater reductions in headache days and disability than a group receiving education control plus AMI. Specifically, we found that CBT combined with AMI improved outcomes for about 2 out of 3 pediatric chronic migraineurs (ages 10-17). Reduction in headache days by ≥ 50% was seen within the first 8 weeks of this 5-month trial (Powers SW, Kashikar-Zuck SM, Allen JR, et al. Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial. JAMA. 2013;310(24):2622-2630). Despite this evidence of efficacy, the mechanisms supporting CBT for migraine remain poorly understood. This lack of mechanistic understanding leaves patients, providers, and payers reluctant to promote CBT as a primary treatment modality. Moreover, opportunities to optimize and individualize CBT remain unrealized because of limited basic understanding by which different components of CBT exert their effects. Little remains known about the specific brain mechanisms by which CBT reduces pain. Therefore, it is critical that we understand how and why CBT may improve headache outcomes in contrast to pill-taking treatments, specifically placebo. Brain imaging and quantitative sensory testing are novel tools to investigate possible mechanisms of CBT, placebo, and medication. In addition understanding the components of CBT and how they may work at the brain and pain processing levels is important. As such, two broad components of CBT represent clear targets for investigation: relaxation and cognitive reappraisal. Evolving consensus in the pain community and at a national level suggests that examining biological mechanisms of how mind and body approaches lead to benefits for patients will advance care, improve outcomes, and legitimize non-pharmacological treatment for pediatric chronic pain. As such, this mechanistic/basic science study seeks to identify the neural mechanisms by which youth with migraine improve in response to preventive treatment. Pediatric medical and behavioral clinicians can use mechanistic insights from this study to provide patients and families with a stronger rationale for treatment, thereby decreasing stigma and increasing confidence in and commitment to the care plan.