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

描述（由申请人提供）：安慰剂和反安慰剂研究都是重要的研究问题，对人类自我愈合和自我伤害具有广泛的影响。安慰剂镇痛和nocebo痛觉过敏是最强大的安慰剂和nocebo效应，这些效应提供了一个独特的例子，如何上下文学习/条件反射可以减轻或加重我们的疼痛体验。以往的研究表明，安慰剂镇痛和反安慰剂痛觉过敏都是由多个脑区和神经递质参与的高度活跃的神经过程引起的。研究还表明，没有单一的神经生物学机制可以解释这两种影响。因此，关键的下一步是进行不同的安慰剂镇痛效果的比较研究，并确定它们如何不同于反安慰剂痛觉过敏，以区分这些重要的临床现象背后的不同神经机制。使用创新的脑成像技术，这项拟议的研究试图解决两个问题：1）阿片类和非阿片类条件反射引起的安慰剂效应的不同脑机制是什么？和2）是否有一个共同的脑网络介导预期诱发的安慰剂镇痛和反安慰剂痛觉过敏？我们的机制研究将比较不同的药理学条件反射范例（包括阿片类和非阿片类条件反射）使用一个集成的MR-PET系统，和不同的经验期望操纵范例（安慰剂镇痛和nocebo痛觉过敏）使用功能磁共振成像。回答这些问题将大大促进我们对安慰剂/反安慰剂效应的理解，促进新方法的开发，（或避免）这些自我愈合（或自我伤害）的能力，告诉我们以前的经验如何有意识地（by expectation）and unconsciously（通过期望）（通过条件反射）塑造我们的大脑反应，并阐明我们对大脑功能，疼痛感知，和疼痛调节。

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.