Neural and psychological mechanisms of pain perception

疼痛可以通过关于治疗的明确信念、先前的经验和学习、支持患者-提供者关系的人际过程以及与治疗环境相关的背景因素来调节。 在这个项目中，我们系统地研究了介导这些因素对急性疼痛的影响的神经和心理机制。 我们专注于期望，注意力，情绪，条件反射/联想学习和社会因素。 我们的实验主要使用功能性磁共振成像（fMRI）和心理生理测量，以及行为分析和自我报告。 我们正在研究不同类型的疼痛相关预期对疼痛决策以及大脑和身体反应的影响。 我们还计划将急性疼痛与其他享乐和知觉过程进行比较。 这将使我们能够区分疼痛感知所特有的过程和那些不特定于疼痛的过程，例如涉及跨领域感知和决策的过程。 这是情感神经科学和疼痛科的第二年，实验室继续发展，增加了一名博士后研究员和两名博士后研究助理。一位前博士后也通过NIH-KI研究生合作项目加入了实验室，担任博士研究员。我们今年的工作重点是对我们的人类受试者方案“疼痛感知的神经和心理机制”的数据收集。“该方案包括五个子研究，旨在a）分离疼痛调制的不同方面，B）比较急性疼痛模式（例如，热痛对电击诱发的疼痛），以及c）将疼痛与其它享乐和感知领域（例如，味道）。在所有的研究中，我们测量了关于疼痛体验的决定（自我报告）以及对引起疼痛的有害刺激的神经和生理反应。 在分析过程中，我们将结合联合收割机计算建模与先进的神经成像分析，以隔离神经和心理机制，介导的期望，注意力和情绪对主观疼痛的影响。 我们的方案要求所有参与者在筛选后进行初始校准。参与者完成问卷调查，然后进行一个程序，测量疼痛等级，以响应有害的热刺激，并确定每个参与者的疼痛阈值和耐受性。迄今为止，已有118人完成了这一程序。我们分析了温度、疼痛和自主神经反应之间的关系，发现自主神经对客观刺激的反应取决于反应是否被归类为疼痛。此外，我们还发现了自我报告的特质正念和回顾性（但不是在线）疼痛报告之间的相关性。 研究员和暑期学生在社会和情感神经科学学会年会以及NIH夏季海报日上展示了这些发现。我们目前正在准备这些发现，以供预计在2017财年初提交的手稿使用。 2016财年标志着我们第一个fMRI子研究的开始，该研究旨在研究经典条件反射和指导知识对疼痛和逆转学习的影响。 30名健康志愿者成功完成了fMRI任务（我们的目标是40人的完整样本）。中期数据由一位学士后研究员在NIH Postbac海报日进行分析和展示。初步分析（结合联合收割机的fMRI数据与我们的行为试点研究的数据）表明，基于线索的预期对疼痛报告和皮肤电导反应的影响之间的分离，并建议反应可能与状态焦虑。 我们还开始了第二个子研究的试点，旨在测试是否线索为基础的预期和治疗为基础的预期（即安慰剂反应）调节疼痛通过分离的途径。 这项研究交叉条件线索与安慰剂镇痛操作。12个人已经完成了行为试点任务的变体，我们能够引出基于线索的预期效应（复制Atlas等人，2010）和安慰剂效应。我们计划再运行5个参与者，然后在将任务调整为fMRI扫描仪之前计算功效分析。功能磁共振成像研究应该在2017财年早期开始开始。 最后，我们与仪器部分合作，建立了一个味觉计（味觉传递装置），可以在功能磁共振成像扫描仪中传递果汁。我们计划研究疼痛和味觉之间的关系，并旨在隔离特定领域以及领域的一般机制，这些机制是期望，情感学习和感知的基础。我们目前正在开发一种与我们的疼痛校准程序平行的校准程序，并确定将在研究期间递送的促味剂浓度。我们预计将在2017财年初开始在健康志愿者中试行该任务的行为版本。

Pain can be modulated by explicit beliefs about treatments, prior experience and learning, interpersonal processes that support the patient-provider relationship, and contextual factors related to the treatment environment. In this project, we systematically investigate the neural and psychological mechanisms that mediate the effects of these factors on acute pain. We focus on expectations, attention, emotion, conditioning/associative learning, and social factors. Our experiments principally use functional magnetic resonance imaging (fMRI) and psychophysiological measurements, as well as behavioral assays and self-reports. We are examining the effects of different types of pain-related expectations on decisions about pain as well as responses in the brain and body. We also plan to compare acute pain with other hedonic and perceptual processes. This will allow us to distinguish processes that are unique to pain perception from those that are not specific to pain, such as processes involved in perception and decision-making across domains. This was the second year of the Section on Affective Neuroscience and Pain, and the lab continued to grow, adding one postdoctoral fellow and two additional postbaccalaureate research assistants. One former postbaccalaureate also joined the lab as a doctoral fellow through the NIH-KI graduate partnership program. Our efforts this year were focused on data collection on our human subjects protocol "Neural and psychological mechanisms of pain perception." The protocol includes five sub-studies designed to a) isolate different aspects of pain modulation, b) compare acute pain modalities (e.g., thermal pain versus shock-induced pain), and c) compare and contrast pain with other hedonic and perceptual domains (e.g., taste). In all studies, we measure decisions about pain experience (self-report) as well as neural and physiological responses to noxious stimuli that cause pain. During analysis, we will combine computational modeling with advanced neuroimaging analyses to isolate the neural and psychological mechanisms that mediate the effects of expectations, attention, and emotion on subjective pain. Our protocol requires all participants to go through an initial calibration session, following screening. Participants complete questionnaires, and then undergo a procedure that measures pain ratings in response to noxious heat stimuli and determines each participants pain threshold and tolerance. 118 individuals have completed this procedure to date. We have analyzed the relationship between temperature, pain, and autonomic responses, and have found that autonomic responses to objective stimuli depend on whether a response is classified as painful or not. Furthermore, we have found correlations between self-reported trait mindfulness and retrospective, but not online, pain reports. Fellows and summer students presented these findings at the Social and Affective Neuroscience Societys annual meeting, as well as NIHs Summer Poster Day. We are currently preparing these findings for manuscript submission anticipated in early in FY17. FY16 marked the start of our first fMRI sub-study, designed to examine the effects of classical conditioning and instructed knowledge on pain and reversal learning. Thirty healthy volunteers have successfully completed the fMRI task (we aim for a full sample of 40 individuals). Interim data were analyzed and presented by one of the postbaccalaureate fellows for NIHs Postbac Poster Day. Preliminary analyses (which combine fMRI data with data from our behavioral pilot study) indicate promising dissociations between cue-based expectancy effects on pain reports and skin conductance responses, and suggest that responses may be related to state anxiety. We also began piloting a second sub-study designed to test whether cue-based expectancies and treatment-based expectancies (i.e. placebo responses) modulate pain through dissociable pathways. This study crosses conditioned cues with a placebo analgesia manipulation. Twelve individuals have completed variants of the behavioral pilot task, and we are able to elicit both cue-based expectancy effects (replicating Atlas et al., 2010) and placebo effects simultaneously. We plan to run 5 more participants and then will compute power analyses prior to adapting the task for the fMRI scanner. The fMRI study should begin in early FY17. Finally, we worked with the Section on Instrumentation to build a gustometer (taste-delivery device) that can deliver juices in the fMRI scanner. We plan to examine the relationship between pain and taste, and aim to isolate domain-specific as well as domain-general mechanisms that underlie expectancy, affective learning, and perception. We are currently developing a calibration procedure that parallels our pain calibration procedure, and determining the tastants concentrations that will be delivered during the study. We expect to begin piloting a behavioral version of the task with healthy volunteers in early FY17.