Neurobiology of Placebo Effects in Fibromyalgia

纤维肌痛安慰剂效应的神经生物学

基本信息

批准号：
8893900
负责人：
Jon-Kar Zubieta
金额：
--
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8893900
关键词：
Absence of pain sensation Accounting Acute Address Affect Affective Amygdaloid structure Analgesics Anterior Biological Biological Markers Brain Brain region Cholecystokinin Clinical Clinical Medicine Clinical Research Clinical Trials Cognitive Complement Consent Cross-Over Trials Crossover Design Data Decision Making Diagnosis Disclosure Dopamine Dorsal Ego Emotional Environment Enzymes Ethics Experimental Models Fibromyalgia Genes Genetic Polymorphism Health Hydrocortisone Individual Individual Differences Inflammatory Intervention Intravenous Laboratories Literature Measurement Measures Mediating Medical Methodology Molecular Nature Neurobiology Neurotic Disorders Neurotransmitters Noise Nucleus Accumbens Opioid Opioid Receptor Pain Patients Persistent pain Personality inventories Pharmaceutical Preparations Pilot Projects Placebo Effect Placebos Plasma Positioning Attribute Positron-Emission Tomography Predictive Value Process Psychophysics Randomized Recommendation Records Recovery Regulation Reporting Rewards Sampling Scanning Science Scientist Sensory Social Environment Source Structure Surrogate Markers Syndrome System Technology Testing Thalamic structure Therapeutic Therapeutic Intervention Time Translating Variant Wit body mechanics chronic pain clinical application clinical practice conditioning cytokine drug development drug discovery endogenous cannabinoid system endogenous opioids expectation fatty acid amide hydrolase healthy volunteer in vivo inter-individual variation midbrain central gray substance molecular imaging neurochemistry neuroimaging neuroregulation neurotransmission novel patient stratification pill potential biomarker psychosocial radiotracer randomized trial receptor response symptomatic improvement therapy development trait treatment response week trial

项目摘要

DESCRIPTION (provided by applicant): Placebo responses represent a substantial source of "noise" in clinical trials. Examination of inter-individual differences in the function of placebo responsive mechanisms, and potential surrogates (biomarkers) would help inform the sources of variability in clinical studies in an objective, mechanistic fashion. The formation of biologica placebo effects also represents a resiliency mechanism, uncovered by the cognitive emotional integration of the expectations created by the treating environment. As such, delineation of these processes would point to biological targets that have not been contemplated in traditional drug or treatment development. Endogenous opioid mechanisms have been centrally implicated in the formation of placebo analgesic effects for more than three-decades, but their function has not been systematically studied in clinical samples. This application examines the integrity of the endogenous opioid system in a sample of patients diagnosed with fibromyalgia (FM), a persistent pain syndrome with moderate placebo responses. We will utilize positron emission tomography (PET) and a selective �-opioid receptor radiotracer to acquire objective molecular measures known to be associated with the formation of placebo analgesic effects in clinical and experimental samples. Measures of �-opioid receptor (�OR) availability at baseline and the activation of this neurotransmitter system in response to a releasing challenge (intravenous placebo with expectation of analgesia) will be examined against treatment response measures in what effectively represents a within- subject, randomized, cross-over trial of placebo pills wit and without expectations of activity. We will utilize non-deceptive consent methodology, following current ethical recommendations and consistent with ongoing studies in our laboratory. It is proposed that baseline �OR availability in vivo and the capacity to activate this neurotransmitter system in the context of positive expectations of improvement experimentally created during scanning and by the administration of placebo during the trial, will be associated with treatment response in FM patients. In the spirit of clinical applicability, these mechanistic, molecular imaging studies of predictors of treatment response in FM will be complemented by the examination of simpler biomarkers. The selected markers have been found associated with endogenous opioid system function, and their predictive value, alone and in combination, will be examined as potential predictors of so-called "non-specific" treatment responses. This proposal assembles a comprehensive team of clinicians and scientists with specialized and complementary expertise, and substantial track records in molecular imaging, chronic pain, FM and clinical trials that is uniquely positioned to manage and complete the studies proposed. It addresses a severe health problem, chronic pain, and a substantial source of variability in clinical studies, biological placebo effects, which has not been systematically studied at a mechanistic level in clinical samples. The data acquired will also point to novel treatment targets not addressed in traditional drug discovery strategies.

描述（由申请人提供）：安慰剂反应是临床试验中“噪音”的重要来源。检查安慰剂反应机制和潜在替代物（生物标志物）功能的个体差异将有助于了解临床变异的来源。以客观、机械的方式进行研究。生物安慰剂效应的形成也代表了一种弹性机制，是由治疗环境所产生的期望的认知情感整合所揭示的。三十多年来，内源性阿片类药物机制一直与安慰剂镇痛作用的形成密切相关，但其功能尚未在临床样本中进行系统研究。该应用程序检查的完整性我们将利用正电子发射断层扫描 (PET) 和选择性 α-阿片受体放射性示踪剂来获取已知相关的客观分子测量结果。在临床和实验样本中形成安慰剂镇痛作用，测量基线时的β-阿片受体（βOR）可用性以及该神经递质系统响应释放挑战的激活。（预期镇痛的静脉安慰剂）将根据治疗反应措施进行检查，这实际上代表了安慰剂药丸的受试者内、随机、交叉试验，并且没有预期的活性。我们将采用非欺骗性同意方法，如下。目前的伦理建议，并与我们实验室正在进行的研究一致，建议在扫描期间和通过安慰剂给药期间实验产生的改善的积极期望的背景下，基线或体内可用性以及激活该神经递质系统的能力。试用，将关联FM 患者的治疗反应本着临床适用性的精神，这些机制， FM 治疗反应预测因子的分子影像研究将通过检查更简单的生物标志物得到补充，已发现选定的标志物与内源性阿片类药物系统功能相关，并且它们的单独和组合的预测价值将作为潜在的预测因子进行检查。该提案汇集了一个由超级明星和科学家组成的综合团队，他们拥有专业且互补的专业知识，并且在分子成像、慢性疼痛、FM 和临床试验方面拥有丰富的跟踪记录，在管理和完成方面具有独特的优势。提出的研究。严重的健康问题、慢性疼痛以及临床研究中变异性的重要来源、生物安慰剂效应尚未在临床样本的机制水平上进行系统研究。所获得的数据也将指出新的治疗目标。传统的药物发现策略中没有解决这一问题。