Brain mechanisms for clinical placebo in chronic pain

描述(由申请者提供)：此应用程序旨在检查慢性背痛患者的安慰剂反应的大脑属性。我们有初步数据表明，在对治疗采取中性指导的盲法临床试验研究中，慢性背痛(CBP)和骨关节炎患者可以细分为安慰剂应答者和无应答者，这些差异可以通过大脑活动预先预测。这些结果表明，CBP安慰剂反应可能具有临床实用价值，其特性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安慰剂反应特性是在双盲临床试验(RCT)环境中研究的。在目标1中，我们将检查CBP患者安慰剂反应倾向的重复性和可预测性。在随机对照试验开始之前和试验期间的不同时间点对大脑解剖和功能进行评估。此外，在整个试验过程中收集了疼痛和生活质量概况，使用智能手机技术监测在自然环境中获取这些参数。脑生物标记物的结果和预测在CBP安慰剂应答者和无应答者之间进行了对比，并与不接受治疗进行了比较。洗脱期用于测试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方法，基于与神经成像生物标记物的相关性来预测安慰剂倾向。总体而言，这些研究旨在临床试验的背景下，对安慰剂止痛治疗慢性疼痛的神经生物学进行批判性评估，并创建一种现成的、临床上有用的工具来识别安慰剂应答者。如果成功，概述的研究的完成将有可能极大地 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.