Molecular and Functional PET-fMRI Measures of Placebo Analgesia in Migraine

描述（由申请人提供）：本申请的目的是使用脑功能（fMRI）和<$-阿片受体可用性（11 C-卡尼坦PET）的同时测量研究无头痛偏头痛患者的安慰剂镇痛。通过研究相关临床人群中的安慰剂效应，我们将获得关于脑功能、化学以及关键的相互作用的独特数据。众所周知，持续性疼痛会改变大脑的结构、功能、连通性和化学物质。此外，持续的慢性疼痛会影响实验疼痛，使得难以解释来自患者群体的结果。差异是由于大脑的改变，还是由于持续的慢性疼痛经历？通过研究发作间期（无头痛）状态的偏头痛患者，我们可以排除后者， 描述与健康大脑相比，在疼痛改变（但无疼痛）的大脑中安慰剂镇痛。通过同时使用fMRI和PET成像，我们将提供关于脑血流变化（fMRI）和内源性阿片样物质释放（PET）如何相互作用以产生安慰剂疼痛减轻的主观体验的新数据。这将提供对安慰剂反应的新水平的理解，并为研究和开发临床安慰剂反应的预测生物标志物奠定基础。 公共卫生相关性：目前安慰剂反应的神经生物学模型依赖于健康受试者的脑功能或化学研究。慢性疼痛改变大脑和安慰剂反应的患者可能有不同的机制。我们将研究偏头痛患者的安慰剂反应，并同时测量脑功能和化学。

DESCRIPTION (provided by applicant): The goal of this application is to study placebo analgesia in headache-free migraine patients using simultaneous measures of brain function (fMRI) and ¿-opioid receptor availability (11C-carnetanil PET). By studying the placebo effect in a relevant clinical population, we will obtain unique data on brain function, chemistry, and, critically, their interaction. It is well established that persistent pain changes bothstructure, function, connectivity and chemistry of the brain. Moreover, ongoing chronic pain influences experimental pain, making interpretations of results derived from patient populations difficult. Are differences due to the altered brain, or due to the ongoing experience of chronic pain? By studying migraine patients in the inter-ictal (headache free) state, we can rule out the latter and describe placebo analgesia in pain-altered (but pain free) brains, as compared to healthy brains. By employing simultaneous fMRI and PET imaging, we will be provide novel data on how brain blood flow changes (fMRI) and endogenous opioid release (PET) interact to create the subjective experience of placebo pain reduction. This will provide a new level of understanding of placebo responses, and lay a foundation for studying and developing predictive biomarkers for clinical placebo responses. PUBLIC HEALTH RELEVANCE: Current neurobiological models of the placebo response rely on studies of either brain function or chemistry in healthy subjects. Chronic pain changes the brain and placebo responses in patients may have different mechanisms. We will study placebo responses in migraine patients and measure brain function and chemistry simultaneously.