Using fMRI to understand response to an integrative treatment for pain and anxiety in pediatric functional abdominal pain disorders (FAPD)

项目摘要 候选人的长期目标是设计有效的和机械知情的非药物干预儿童功能性腹痛障碍(FAPD)。候选人的初步研究表明，FAPD中焦虑的增加与更大的疼痛和残疾有关，而焦虑对标准认知行为疗法(CBT)治疗疼痛的反应有不利影响。因此，候选人制定了减少焦虑和疼痛治疗的目标(Adapt；F32 HD078049)，这是一种有希望的儿科FAPD疼痛和焦虑管理干预措施。互补的方法，如正念冥想，可能会进一步减少疼痛和焦虑。在这项建议中，PI将正念冥想与Adapt协议中的传统方法相结合，以进一步改善患者的结果。除了开发有效的综合治疗方法外，候选人的目标是了解治疗效果的机制。在这项拟议的研究中，候选人将研究儿童FAPD综合干预所涉及的大脑机制。患有FAPD和共病焦虑的患者将接受fMRI检查，以探索适应后内脏疼痛诱导(通过水负荷症状激发任务；WL-SPT)的反应与等待名单对照条件的差异。在目标1中，有人提出，在适应后的WL-SPT期间，年轻人将显示杏仁核和前额叶皮质之间的过度连接减少。在目标2中，与对疼痛诱导的主观反应相关的大脑激活预计在完成适应的年轻人中会减少。常规的血氧水平依赖(BOLD)功能磁共振成像将被用来评估功能连接，以捕捉活动的时刻波动。动脉自旋标记核磁共振技术将被用来推断局部大脑活动，因为这些激活代表着相对稳定的状态。根据NCCIH的资金优先顺序，这项研究试图增加对非药物治疗方法影响慢性疼痛和焦虑临床结果的机制的理解。结果将通过提供完善和测试针对FPD和共病焦虑的量身定制干预所需的关键信息来推动该领域的发展--候选人的长期职业目标。在这项建议中，候选人将利用在儿科慢性疼痛和焦虑方面的培训和专业知识，在一个强大的指导团队的指导下，研究儿科FAPD治疗反应的大脑机制。为了成功地执行这项研究并为独立的研究生涯做准备，候选人将接受以下方面的广泛培训：1)以正念冥想为重点的慢性疼痛和焦虑的补充治疗；2)脑功能成像；3)高级统计学。这项建议将使候选人能够对FAPD的治疗反应机制有一个成熟的了解，并制定一个独特的研究计划。结果将允许候选人作为一名综合医学研究人员在患有慢性疼痛的青年中测试量身定制的非药物干预措施。

Project Summary The candidate’s long-term objectives are to devise effective and mechanistically-informed nonpharmacological interventions for pediatric functional abdominal pain disorders (FAPD). The candidate’s pilot studies have shown that increased anxiety in FAPD is associated with greater pain and disability, and anxiety adversely impacts response to standard cognitive behavioral therapy (CBT) for pain. Thus, the candidate developed the Aim to Decrease Anxiety and Pain Treatment (ADAPT; F32 HD078049), a promising intervention for the management of pain and anxiety in pediatric FAPD. Complementary approaches, such as mindfulness meditation, may further reduce pain and anxiety. In this proposal, the PI integrates mindfulness meditation with conventional approaches in the ADAPT protocol to further improve patient outcomes. In addition to developing effective integrative treatments, the candidate aims to understand the mechanisms of treatment effects. For the proposed study, the candidate will investigate brain mechanisms that are implicated in response to an integrative intervention for pediatric FAPD. Patients with FAPD and comorbid anxiety will undergo an fMRI to explore differences in response to visceral pain induction (via the water load symptom provocation task; WL-SPT) after ADAPT as compared to a waitlist control condition. In Aim 1, it is proposed that youth will show reduced hyperconnectivity between the amygdala and prefrontal cortex during the WL-SPT following ADAPT. In Aim 2, brain activations associated with a subjective response to pain induction are expected to diminish in youth who have completed ADAPT. Conventional blood oxygenation level dependent (BOLD) fMRI will be used to assess functional connectivity to capture moment-to-moment fluctuations in activity. The arterial spin label MRI technique will be used to gain inferences into regional brain activity since these activations represent a relatively steady-state. In line with the NCCIH funding priorities, this study seeks to increase understanding of the mechanisms through which nonpharmacological treatment approaches impact clinical outcomes in chronic pain and anxiety. Results will advance the field by providing crucial information needed for the refinement and testing of a tailored intervention for FAPD and comorbid anxiety - the candidate’s long-term career goal. In this proposal, the candidate will draw upon training and expertise in pediatric chronic pain and anxiety to investigate brain mechanisms of treatment response in pediatric FAPD under the guidance of a strong mentorship team. To successfully execute this research and prepare for an independent research career, the candidate will undergo extensive training in 1) complementary treatments for chronic pain and anxiety with a focus on mindfulness meditation, 2) functional brain imaging, and 3) advanced statistics. This proposal will enable the candidate to develop a sophisticated understanding of the mechanisms of treatment response in FAPD and develop a unique program of research. Results will allow the candidate to test tailored nonpharmacological interventions in youth with chronic pain as an integrative medicine researcher.