FMRI-based Decoupling of Conditioning and Belief Effects on Placebo Analgesia

描述(由申请人提供)：该项目旨在区分安慰剂止痛的神经机制。目前，许多研究人员已经得出结论，安慰剂止痛主要取决于个人对治疗的信念，但替代证据表明，其他较低水平的过程可能参与了与信念无关的止痛。在这项拟议的研究中，对安慰剂治疗的信念将通过受试者内部的口头信息来操纵，而经验和信念将通过受试者之间的条件反射来操纵。这项拟议的研究将把言语信息对安慰剂止痛的影响与通过经验学到的隐性价值分开。受试者被要求相信安慰剂治疗在减轻疼痛方面是有效的，方法是首先接受一系列高温疼痛刺激，然后在实验者使用带有止痛说明的安慰剂乳膏后，再接受第二系列低温疼痛刺激。一半的受试者将经历一次单一的条件反射训练(短时条件组)，另一半的受试者将在不同的日子进行四次单独的训练(长条件组)。对于所有受试者，安慰剂效应将在最后的条件训练后在扫描仪中进行测试。在测试过程中，受试者将对使用和不使用安慰剂乳膏的中温疼痛刺激的疼痛程度进行评级。然后，受试者将被告知他们接受的治疗是安慰剂，并将被要求再次评估使用和不使用安慰剂乳膏的中温疼痛刺激的疼痛程度。揭示治疗的性质可以比较不同信念水平下基于fMRI的疼痛活动，并可以根据受试者接受的条件反射程度进行跨组比较。该项目的fMRI分析将专注于分离语言信息和经验在与疼痛相关的大脑区域之间的影响，以及大脑激活、疼痛和对治疗的信念之间的关系是否因接受的训练量而不同。我们预计，额叶疼痛区域的疼痛相关活动，包括眼眶额叶和前扣带回皮质，将取决于对治疗的信念，以及较低级别区域的疼痛相关活动，如导水管周围灰质和轮状腹内侧髓质，将取决于受试者接受的条件反射数量。我们将使用分类技术来预测在安慰剂治疗被揭示后，哪些受试者将继续经历安慰剂止痛。我们希望发现，低阶疼痛区域的激活可以预测受试者在暴露后是否继续体验安慰剂止痛。本研究将为镇痛和止痛提供一种新的思路。如果发现了安慰剂止痛的多种途径，将提出新的治疗方法和方法，以改进现有的止痛治疗，使用条件反射来辅助体内的自然止痛系统。 与公共健康相关：这个项目将研究管理疼痛缓解的大脑系统的差异。这项研究将重点放在涉及疼痛缓解的大脑区域，测试特定区域的活动是否可以预测安慰剂治疗的有效性。结果是 这项研究的结论可能会建议使用安慰剂来缓解疼痛的各种程序，即使他们知道治疗是安慰剂。

DESCRIPTION (provided by applicant): This project aims to differentiate between neural mechanisms that underlie placebo analgesia. Currently, many researchers have concluded that placebo analgesia depends primarily on an individual's belief in a treatment, but alternative evidence suggests that other lower level processes may be involved in analgesia that are dissociable from belief. In the proposed study, belief in a placebo treatment will be manipulated using verbal information within subjects, and both experience and belief will be manipulated using conditioning between subjects. The proposed study will separate the effect of verbal information on placebo analgesia from implicit values learned through experience. Subjects are conditioned to believe that a placebo treatment is effective at reducing pain by first receiving a series of high-temperature painful stimulations, and then receiving a second series of low- temperature painful stimuli after the experimenter applies a placebo cream with instructions that it will reduce pain. Half of the subjects will experience a single conditioning session (short conditioning group), and the other half will have four separate sessions on different days (long conditioning group). For all subjects, the placebo effect will be tested in the scanner after the final conditioning session. During testing, subjects will rate the painfulness of medium-temperature painful stimuli with and without the placebo cream. Subjects will then be informed that the treatment they received was a placebo, and will be asked to again rate the painfulness of medium-temperature painful stimuli with and without the placebo cream. Revealing the nature of the treatment allows comparison of fMRI based pain activity at different levels of belief, and allows comparison across groups of subjects depending on how much conditioning they received. FMRI analysis for this project will focus on dissociating the effects of verbal information and experience among pain related brain regions, and whether the relationship between brain activation, pain, and the belief in a treatment is different depending on the amount of training received. We anticipate that pain-related activity in frontal pain areas, including the orbitofrontal and anterior cingulate cortices, will depend on belief in the treatment and that pain-related activity in lower order areas, such as the periaqueductal gray and rostroventromedial medulla, will depend on the amount of conditioning subjects receive. We will use classification techniques to predict which subjects will continue to experience placebo analgesia after the placebo treatment is revealed. We expect to find that activation in the lower order pain regions predicts whether subjects continue to experience placebo analgesia after the reveal. This research will provide a new way of thinking about analgesia and pain relief. If multiple pathways for placebo analgesia are found, it would suggest novel treatments and methods for improving existing pain relief treatments using conditioning to assist the natural pain relief system in the body. PUBLIC HEALTH RELEVANCE: This project will examine differences in brain systems governing pain relief. This study will focus on brain regions involved in pain relief, testing whether activity in specific regions predicts the effectiveness of a placebo treatment. The results of this study may suggest various procedures to use placebos to give people pain relief, even if they know the treatment is a placebo.