Brain mechanisms for clinical placebo in chronic pain

描述（由申请人提供）：该应用程序旨在检查慢性背痛患者安慰剂反应的大脑特性。我们有初步数据表明，在盲法临床试验研究中，关于治疗的说明是中性的，慢性背痛（CBP）和骨关节炎患者可以细分为安慰剂应答者和非应答者，这些差异可以通过大脑活动先验预测。结果表明，CBP安慰剂反应可能具有临床实用性，其性质可以通过人脑成像技术进行研究。我们在三个具体目标中解决这些问题，其中CBP安慰剂反应特性在双盲临床试验（RCT）中进行了研究。在目标1中，我们将检查CBP患者中安慰剂反应倾向的可重复性和可预测性。在RCT开始之前和试验期间的不同时间点评估脑解剖结构和功能。此外，在整个试验过程中收集疼痛和生活质量概况，使用智能手机技术监测以在自然环境中获取这些参数。对比CBP安慰剂应答者和无应答者之间的脑生物标志物结局和预测，并与无治疗进行比较。洗脱期用于检测安慰剂反应的可逆性。在目标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，我们开发了一种自我报告措施，根据与神经成像生物标志物的相关性来预测安慰剂倾向。总体而言，这些研究旨在严格评估临床试验背景下安慰剂镇痛治疗慢性疼痛的神经生物学，并创建一个易于获得的临床有用工具来识别安慰剂应答者。如果成功，完成概述的研究有可能大大提高 改变慢性疼痛的医疗保健。

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.