The Neurobiology of Placebo and Nocebo Effects: A Brain Imaging Study

描述(由申请人提供)：安慰剂和非西比妥研究都是重要的研究问题，对人类的自我修复和自我伤害具有广泛的影响。安慰剂止痛和痛觉过敏是最强烈的安慰剂和非安慰剂效应，这些效应提供了一个独特的例子，说明背景学习/条件反射如何缓解或加剧我们的疼痛体验。以往的研究表明，安慰剂止痛和非安慰剂痛觉过敏都源于涉及多个脑区和神经递质的高度活跃的神经过程。研究还表明，没有一种单一的神经生物学机制可以解释这两种影响。因此，关键的下一步是对不同的安慰剂止痛效果进行比较研究，并确定它们与非安慰剂痛敏的不同之处，以便区分这些重要临床现象背后的不同神经机制。使用一种创新的脑成像技术，这项拟议的研究试图解决两个问题：1)阿片类药物和非阿片类药物条件作用产生安慰剂效应的不同大脑机制是什么？2)共同的大脑网络是否介导了预期诱发的安慰剂止痛和非预期痛觉过敏？我们的机制研究将使用集成的MR-PET系统来比较不同的药物条件反射范式(包括阿片类药物和非阿片类药物的条件作用)，以及使用功能磁共振成像来比较不同的经验预期操作范式(安慰剂止痛和非阿片类药物过敏)。回答这些问题将极大地促进我们对安慰剂/非安慰剂效应的理解，促进开发利用(或避免)这些自我修复(或自我伤害)能力的新方法，告知我们以前的经验如何有意识(通过预期)和无意识(通过条件作用)塑造我们的大脑反应，并阐明我们对大脑功能、疼痛感知和疼痛调制的基本原理的理解。

DESCRIPTION (provided by applicant): Both placebo and nocebo studies are important research issues with broad implications for human self-healing and self-harming. Placebo analgesia and nocebo hyperalgesia are the most robust placebo and nocebo effects, and these effects provide a unique example of how contextual learning/conditioning can either relieve or aggravate our pain experience. Previous studies have demonstrated that both placebo analgesia and nocebo hyperalgesia derive from highly active neural process involving multiple brain regions and neurotransmitters. Studies also indicate that no single neurobiological mechanism can explain both effects. Thus, the crucial next step is to perform comparative studies of different placebo analgesia effects and ascertain how they differ from nocebo hyperalgesia in order to distinguish the different neural mechanisms underlying these important clinical phenomena. Using an innovative brain imaging technique, this proposed study attempts to address two questions: 1) what are the distinct brain mechanisms of placebo effects due to opioid and non-opioid conditioning? and 2) Does a common brain network mediate expectancy-evoked placebo analgesia and nocebo hyperalgesia? Our mechanistic investigation will compare different pharmacological conditioning paradigms (including opioid and non-opioid conditioning) using an integrated MR-PET system, and different experiential expectancy manipulation paradigms (placebo analgesia and nocebo hyperalgesia) using fMRI. Answering these questions will significantly advance our understanding of placebo/nocebo effects, facilitate the development of new methods to harness (or avoid) these self- healing (or self-harming) capacities, inform us on how previous experiences can consciously (by expectation) and unconsciously (by conditioning) sculpt our brain response, and shed light on our understanding of basic principles of brain function, pain perception, and pain modulation.