Neural and psychological mechanisms of pain perception

疼痛可以由对治疗的明确信念、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，我们系统地研究了这些因素对急性疼痛的影响的神经和心理机制。我们关注期望、注意力、情绪、条件性/联想学习和社会因素。我们的实验主要使用功能磁共振成像(FMRI)和心理生理学测量，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关于疼痛的决定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性和知觉过程进行比较。这将使我们能够区分疼痛感知特有的过程和非疼痛特有的过程，例如跨域的感知和决策过程。 这是我们的第一年，我们专注于建立实验室(情感神经科学和疼痛部门)并开始收集数据。人类受试者协议“疼痛感知的神经和心理机制”获得了NINDS协议执行审查委员会和机构审查委员会的批准。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)比较急性疼痛形式(例如，热疼痛与休克诱导的疼痛)，以及c)比较疼痛与其他享乐和感知领域(例如，味觉)。在所有研究中，我们测量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，我们将结合计算建模和高级神经成像分析来分离神经和心理机制，这些机制调节预期、注意力和情绪对主观疼痛的影响。 在方案审批过程中，我们聘请了实验室人员，建立了实验室标准，并在门诊中心开发了我们的实验室。我们现在可以施加有害的热刺激(根据每个人的疼痛敏感度进行校准)，同时收集生理反应，包括瞳孔直径、皮肤电导、心率(通过心电图和外周脉搏)和呼吸。我们的电脑任务是根据患者的眼球运动自行调整速度的，这使得我们可以在任务中使用凝视位置作为额外的依赖测量。 数据收集工作已于今年5月开始。我们已经完成了对23名健康志愿者的测试，他们作为行为飞行员参与了我们的第一个子研究。筛查后，所有参与者都完成了问卷调查，然后进行疼痛校准程序，测量对有害热刺激的疼痛评级，并确定每个参与者的疼痛阈值和耐受性。然后，参与者继续进行一项试验性的子研究，旨在检查经典条件反射和传授知识对疼痛和反转学习的影响。我们的行为子研究的数据用于在功能磁共振扫描之前的任务开发，以及用于效果大小估计和功率分析。 三名暑期学生分析了这些最初试点对象的数据。我们对疼痛校准数据的初步分析表明，a)我们的健康志愿者显示出伤害性刺激温度与报告的疼痛之间的统计关系；2)瞳孔直径与伤害性高温和主观疼痛报告相关；3)皮肤电导反应幅度与伤害性高温和主观疼痛相关。对我们的行为试点数据的初步分析表明，基于线索的预期效应对疼痛报告和皮肤电导反应之间可能存在分离。我们的目标是在我们目前第一个子研究的变体中再收集四个试点参与者，然后将估计我们的效果大小并执行功率分析，以确定fMRI子研究的样本量。我们预计第一个fMRI子研究将在几周内开始，即2015财年结束或2016财年开始。

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 our first year, and we focused on setting up the lab (the Section on Affective Neuroscience and Pain) and beginning data collection. The human subjects protocol "Neural and psychological mechanisms of pain perception" received approval from the NINDS Protocol Implementation Review Committee and the Institutional Review Board. 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. During the protocol approval process, we hired lab personnel, established laboratory standards, and developed our experiment room in the Outpatient Center. We can now administer noxious thermal stimuli (calibrated to each individuals pain sensitivity) while simultaneously collecting physiological responses, including pupil diameter, skin conductance, heart rate (via electrocardiogram and peripheral pulse) and respiration. Our computer tasks are self-paced based on patient eye movements, which allows us to use gaze position as an additional dependent measure in our tasks. Data collection commenced in May of this year. We have completed testing on 23 healthy volunteers who participated as behavioral pilots in our first sub-study. Following screening, all participants completed questionnaires, followed by a pain calibration procedure that measures pain ratings in response to noxious heat stimuli and determines each participants pain threshold and tolerance. Participants then went on to a pilot sub-study designed to examine the effects of classical conditioning and instructed knowledge on pain and reversal learning. Data from our behavioral sub-studies are used for task development prior to fMRI scanning, as well as for effect size estimation and power analysis. Three summer students analyzed data from these initial pilot subjects. Preliminary analyses of our data from the pain calibration indicate that a) our healthy volunteers show statistical relationships between noxious stimulus temperature and reported pain; 2) pupil diameter is correlated with noxious heat and subjective pain reports; 3) skin conductance response amplitude correlates with noxious heat and subjective pain. Preliminary analyses of our behavioral pilot data indicate possible dissociations between cue-based expectancy effects on pain reports and skin conductance responses. We aim to collect four more pilot participants in our current variant of the first sub-study, and then will estimate our effect size and perform power analyses to determine sample size for the fMRI sub-study. We anticipate the first fMRI sub-study will begin in several weeks, at the end of FY15 or the start of FY16.