Pain-related Brain Mechanisms for Pain Catastrophizing Behavior in Response to Home-based Mindfulness-based Meditation Paired with Transcranial Direct Current Stimulation

摘要 这一以行动为重点的机制补充项目的长期目标是开发一个全面的 了解患者如何对疼痛相关行为进行神经控制，从而减少临床 使用基于家庭的非药物疼痛治疗的老年人的疼痛和改善健康结果 接近了。基于疼痛的行为激活和抑制系统模型来解释与疼痛相关的 行为，本附录将评估解释疼痛灾难性行为的潜在大脑机制 老年膝骨性关节炎患者家庭非药物性疼痛干预后的变化 (办公自动化)。目前，美国有1400多万成年人患有有症状的骨性关节炎，这是 慢性疼痛的主要原因。在家长研究(R01NR019051)中，我们进行了双盲， 随机、假对照II期平行组(由2x2析因设计确定的四组1：1：1：1) 临床试验确定远程监督正念冥想(MBM)与 居家经颅直流电刺激对老年抑郁症患者临床疼痛和症状的影响 有症状的膝骨性关节炎。母公司的研究最初并没有提出机械性的临床试验，而这 补充研究将为疼痛相关行为改变提供宝贵的机械性脑成像数据 建立在我们父母研究的基础上。最近的文献表明，临床疼痛与疼痛有关。 灾变行为和功能磁共振成像(FMRI)成像反应 膝骨性关节炎患者疼痛相关脑功能的更大不适应变化(例如，更大的变化 静息和疼痛诱发的脑血流位于扣带回、脑岛、丘脑、杏仁核、中脑导水管周围灰质和 壳核)。综上所述，在这项补充研究中，我们将收集疼痛灾难性行为和fMRI 40名患有膝骨性关节炎的老年人的资料，他们将在下一年在父母研究中招募 使用父项目的现有设计和招聘计划。中心假设是以家庭为基础的 MBM和tDCs配对将减少疼痛相关脑功能的不良适应变化，这将预测疼痛 灾害性行为和临床疼痛。这一假设将通过追求以下具体情况来检验 目的：评价MBM与tDCs配伍对疼痛相关脑功能的影响(由fMRI数据量化)。 在患有膝骨性关节炎的老年人中(特定目标1)；并评估疼痛相关脑之间的关系 功能(通过功能磁共振数据量化)和疼痛灾难性行为和与骨性关节炎相关的临床疼痛(特定目标 2)。这项拟议的研究具有重要意义，因为这项补充研究预计将揭示未被探索的 因果过程(即，通过功能连接改变的与疼痛相关的大脑功能)可以阐明 干预的作用机制。

ABSTRACT The long-term goal of this mechanism of action-focused supplement project is to develop a comprehensive understanding of how patients exert neural control over pain-related behaviors, leading to reductions in clinical pain and improved health outcomes for older adults using home-based nonpharmacological pain management approaches. Based on a behavioral activation and inhibition systems model of pain that explains pain-related behavior, this supplement will assess underlying brain mechanisms explaining pain catastrophizing behavior change following home-based nonpharmacological pain interventions in older adults with knee osteoarthritis (OA). Currently more than 14 million adults in the United States are living with symptomatic OA, one of the leading causes of chronic pain. In the parent study (R01NR019051), we are conducting a double-blind, randomized, sham-controlled phase II parallel group (1:1:1:1 for four groups defined by 2x2 factorial design) clinical trial to determine the effects of remotely supervised Mindfulness-based Meditation (MBM) paired with Transcranial Direct Current Stimulation (tDCS) at home on clinical pain and symptoms in older adults with symptomatic knee OA. The parent study did not originally posit a mechanistic clinical trial, and this supplemental study will provide invaluable mechanistic brain imaging data for pain-related behavior change building on our parent study. Recently, literatures showed that clinical pain is associated with pain catastrophizing behavior and that functional magnetic resonance imaging (fMRI) imaging responses suggested greater maladaptive changes in pain-related brain function in patients with knee OA (e.g., greater changes in resting and pain-evoked cerebral blood flow in cingulate, insula, thalamus, amygdala, periaqueductal gray, and putamen). Taken together, in this supplement study, we will collect pain catastrophizing behavior and fMRI data among 40 older adults with knee OA who will be recruited in the subsequent year in the parent study using the parent project’s existing design and recruitment plan. The central hypothesis is that home-based MBM paired with tDCS will decrease maladaptive changes in pain-related brain function, which will predict pain catastrophizing behavior and clinical pain. This hypothesis will be tested by pursuing the following specific aims: To evaluate the effects of MBM paired with tDCS on pain-related brain function (quantified by fMRI data) in older adults with knee OA (specific aim 1); and to evaluate the relationship between pain-related brain function (quantified by fMRI data) and pain catastrophizing behavior and OA-related clinical pain (specific aim 2). The proposed research is significant because this supplement study is expected to reveal underexplored causal processes (i.e., pain-related brain function via functional connectivity alterations) that can illuminate the intervention’s mechanisms of actions.