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背后的神经机制。目前，许多研究人员得出结论，安慰剂镇痛主要取决于个体对治疗的信念，但其他证据表明，镇痛可能涉及与信念分离的其他较低水平的过程。在拟议的研究中，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。本研究将口头信息对安慰剂镇痛的影响与通过经验习得的内隐价值分离开来。受试者习惯于通过首先接受一系列高温疼痛刺激，然后在实验者涂上安慰剂霜并说明它会减轻疼痛后接受第二组低温疼痛刺激，从而有效地减轻疼痛。一半的受试者将经历一次单一的条件反射（短条件反射组），另一半将在不同的日子里进行四次单独的条件反射（长条件反射组）。对于所有的受试者，安慰剂效应将在最后的条件反射后在扫描仪中进行测试。在测试过程中，受试者将在使用和不使用安慰剂软膏的情况下对中等温度疼痛刺激的疼痛程度进行评分。然后，受试者将被告知他们接受的治疗是安慰剂，并被要求再次对中温疼痛刺激的疼痛程度进行评分，其中有安慰剂霜和没有安慰剂霜。揭示治疗的本质可以在不同的信念水平上比较基于fMRI的疼痛活动，并且可以根据他们接受的条件反射进行跨组的比较。这个项目的FMRI分析将集中在分离语言信息和疼痛相关大脑区域的经验的影响，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（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，而低阶区域（如导水管周围灰质和前腹内侧髓质）的疼痛相关活动将取决于受试者接受条件反射的数量。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经历安慰剂镇痛。我们期望发现，低阶疼痛区域的激活可以预测受试者在揭示后是否会继续经历安慰剂镇痛。本研究将为镇痛和缓解疼痛提供新的思路。如果安慰剂镇痛的多种途径被发现，它将为改善现有的疼痛缓解治疗提供新的治疗方法和方法，利用调节来辅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.