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

描述（由申请人提供）：本项目旨在区分安慰剂镇痛的神经机制。目前，许多研究人员得出的结论是，安慰剂镇痛主要取决于个人的信念，在治疗，但替代证据表明，其他较低水平的过程可能涉及镇痛是分离的信念。在拟定的研究中，将使用受试者内的口头信息操纵对安慰剂治疗的信念，并使用受试者之间的条件反射操纵经验和信念。这项拟议的研究将把口头信息对安慰剂镇痛的影响与通过经验学到的隐性价值分开。受试者通过首先接受一系列高温疼痛刺激，然后在实验者施用具有减轻疼痛说明的安慰剂乳膏后接受第二系列低温疼痛刺激，从而习惯性地相信安慰剂治疗在减轻疼痛方面是有效的。一半的受试者将经历一次调节训练（短调节训练组），另一半将在不同的日子经历四次单独的训练（长调节训练组）。对于所有受试者，将在最后一次调节治疗后在扫描仪中检测安慰剂效应。在测试过程中，受试者将评估有和没有安慰剂乳膏的中温疼痛刺激的疼痛程度。然后将告知受试者他们接受的治疗是安慰剂，并将要求受试者再次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分。揭示治疗的性质允许在不同的信念水平下比较基于fMRI的疼痛活动，并允许根据受试者接受的条件反射程度进行跨组比较。该项目的功能磁共振成像分析将集中在分离疼痛相关脑区之间的言语信息和经验的影响，以及大脑激活，疼痛和治疗信念之间的关系是否因接受的训练量而异。我们预计，额叶疼痛区域（包括眶额皮质和前扣带皮质）的疼痛相关活动将取决于对治疗的信念，而较低级区域（如导水管周围灰质和延髓吻腹内侧区）的疼痛相关活动将取决于受试者接受的条件反射量。我们将使用分类技术来预测哪些受试者将在安慰剂治疗后继续接受安慰剂镇痛。我们希望发现，激活在较低的顺序疼痛区域预测是否受试者继续经历安慰剂镇痛后，揭示。该研究将为镇痛和缓解疼痛提供一种新的思路。如果发现安慰剂镇痛的多种途径，它将提出新的治疗方法和方法，用于改善现有的疼痛缓解治疗，使用条件反射来帮助体内的自然疼痛缓解系统。

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.