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

摘要 这一注重行动机制的补充项目的长期目标是， 了解患者如何对疼痛相关行为施加神经控制，从而减少临床 使用家庭非药物疼痛管理的老年人的疼痛和改善的健康结果 接近。基于疼痛的行为激活和抑制系统模型，该模型解释了疼痛相关的 行为，这种补充将评估潜在的大脑机制解释疼痛灾难化的行为 老年膝关节骨关节炎患者接受家庭非药物疼痛干预后的变化 （OA）。目前，美国有超过1400万成年人患有有症状的OA，这是最常见的疾病之一。 慢性疼痛的主要原因。在母研究（R01NR019051）中，我们正在进行一项双盲， 随机化、假手术对照II期平行组（通过2x2析因设计定义的4个组为1：1：1：1） 临床试验，以确定远程监督的正念冥想（MBM）与 经颅直流电刺激（tDCS）在家中对老年人临床疼痛和症状的影响 症状性膝关节OA。母研究最初并不是机械临床试验， 补充研究将为疼痛相关行为改变提供宝贵的脑成像数据 建立在我们父母研究的基础上近年来，文献表明，临床疼痛与疼痛有关 功能性磁共振成像（fMRI）成像反应表明， 膝关节OA患者疼痛相关脑功能的更大适应不良变化（例如，更大的变化 静息和疼痛诱发的扣带回、丘脑、杏仁核、导水管周围灰质和 壳核）。总之，在这项补充研究中，我们将收集疼痛灾难化行为和功能磁共振成像 在母研究的下一年招募的40名膝关节OA老年人的数据 使用父项目的现有设计和招聘计划。核心假设是， MBM与tDCS配对将减少疼痛相关脑功能的适应不良变化，这将预测疼痛 灾难性行为和临床疼痛。这一假设将通过以下具体的研究加以检验： 目的：评价MBM与tDCS配对对疼痛相关脑功能的影响（通过fMRI数据量化） 在患有膝关节OA的老年人中（具体目标1）;并评估疼痛相关脑 功能（通过fMRI数据量化）和疼痛灾难化行为以及OA相关的临床疼痛（特定目的 2）。拟议的研究意义重大，因为这项补充研究有望揭示未充分探索的 因果过程（即，疼痛相关的脑功能通过功能连接改变），可以照亮 干预的机制。

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.