Brain mechanisms for clinical placebo in chronic pain

描述（由申请人提供）：本应用程序旨在检查慢性背痛患者安慰剂反应的脑特性。我们有初步的数据表明，在盲法临床试验研究中，关于治疗的中性说明，慢性背痛（CBP）和骨关节炎患者可以细分为安慰剂反应者和无反应者，这些差异可以通过大脑活动先验地预测。结果表明，CBP安慰剂反应可能具有临床应用价值，其特性可通过人脑成像技术进行研究。我们在三个特定目标中解决这些问题，其中在双盲临床试验（RCT）环境中研究了CBP安慰剂反应特性。在目的1中，我们将检验CBP患者安慰剂反应倾向的可重复性和可预测性。在随机对照试验开始前和试验期间的不同时间点评估脑解剖和功能。此外，在整个试验过程中收集疼痛和生活质量资料，使用智能手机技术监测在自然环境中获取这些参数。脑生物标志物的结果和预测在CBP安慰剂反应者和无反应者之间进行对比，并与未治疗进行比较。洗脱期用于测试安慰剂反应的可逆性。在Aim 2中，我们研究了安慰剂和药物治疗之间的相互作用，并验证了CBP中安慰剂倾向的可预测性。在目标3中，我们开发了一种基于神经成像生物标志物相关性的自我报告测量来预测安慰剂倾向。总的来说，这些研究的目的是在临床试验的背景下严格评估安慰剂镇痛对慢性疼痛的神经生物学作用，并创建一个易于获得的临床有用的工具来识别安慰剂反应。如果成功，完成概述的研究有可能显著

DESCRIPTION (provided by applicant): This application is designed to examine brain properties for placebo responses in chronic back pain patients. We have preliminary data indicating that, in blinded clinical trial studies with neutral instructions regarding treatment, chronic back pain (CBP) and osteoarthritis patients can be subdivided into placebo responders and non- responders and these differences are PREDICTABLE a priori by brain activity. The results imply that CBP placebo response may have clinical utility and that its properties can be studied by human brain imaging techniques. We address these issues in three specific aims, where CBP placebo response properties are studied in a double blind clinical trial (RCT) setting. In Aim 1, we will examine the reproducibility and predictability of the propensity to placebo response in CBP patients. Brain anatomy and function are assessed prior to the start of the RCTs and at different time points during the trial. Additionally, pain and quality of life profilesare collected throughout the trial, using smart phone technology monitoring to acquire these parameters in a naturalistic setting. Brain biomarker outcomes and predictions are contrasted between CBP placebo responders and non- responders, and compared to no treatment. Washout periods are used to test for reversibility of placebo responses. In Aim 2, we study the interaction between placebo and medication treatment, and validate the predictability of placebo propensity in CBP. In Aim 3, we develop a self-report measure to predict placebo propensity based on correlations with neuro-imaging biomarkers. Overall, these studies are designed to critically assess the neurobiology of placebo analgesia for chronic pain within the setting of clinical trials, and creating a readily available clinically useful instrument to identify placebo responders. If successful, the completion of the outlined studies has the potential to dramatically alter health care in chronic pain.