Neural correlates of hypoalgesia driven by observation

观察驱动的痛觉减退的神经相关性

• 批准号: 10452769
• 负责人: Luana Colloca
• 金额: $ 71.79万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452769
• 关键词: Absence of pain sensation; Acute; Acute Pain; Acute pain management; Address; Adjuvant; Affect; Analgesics; Behavior; Behavioral; Birth; Blood; Brain; Brain Mapping; Brain region; Chronic; Clinical Trials; Clip; Cognition; Cognitive; Color; Cues; Data; Development; Electroencephalogram; Electroencephalography; Empathy; Event; Expectancy; Exposure to; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Healthcare; Immersion; Individual; Inferior; Irritable Bowel Syndrome; Knee Osteoarthritis; Knowledge; Laboratories; Laboratory Research; Learning; Left; Low Back Pain; Marketing; Maryland; Measurement; Measures; Mental Processes; Migraine; Naloxone; Neurobiology; Opioid; Opioid Antagonist; Pain; Pain Research; Pain management; Parietal; Parietal Lobe; Participant; Peripheral; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacology; Physiological; Placebo Control; Placebo Effect; Placebos; Prefrontal Cortex; Process; Psyche structure; Research; Resolution; Resources; Role; Route; Science; Sensory; Signal Transduction; Solid; Suggestion; System; Techniques; Temporal Lobe; Testing; Therapeutic; Universities; attentional control; base; behavioral outcome; chronic pain; clinical pain; clinical practice; conditioning; design; emotional experience; endogenous opioids; expectation; experience; experimental study; fascinate; functional magnetic resonance imaging/electroencephalography; healing; imaging approach; imaging study; innovation; mental state; neural correlate; neurobiological mechanism; neuromechanism; novel; opioid epidemic; opioid user; pain perception; pain reduction; pain relief; pain symptom; painful neuropathy; pill; placebo analgesia; prescription opioid; relating to nervous system; response; side effect; social; social learning; tool; treatment effect; virtual reality; virtual reality environment

Project Summary Placebo effects held an ambivalent place in health care for at least two centuries. On the one hand, placebos are traditionally used as controls in clinical trials to correct for biases and the placebo response is viewed as an effect to be factored out in order to isolate and accurately measure the effects of the treatment. On the other hand, there is scientific evidence that placebo effects represent fascinating psychoneurobiological events involving the contribution of distinct central nervous as well as peripheral physiological mechanisms that influence pain perception and clinical pain symptoms and substantially modulate the response to pain therapeutics. Therefore, placebo effects have shifted from being a challenge for clinical trials to a resource to trigger the reduction of pain based on endogenous mechanisms that can be activated in the brain to promote hypolagesia, self-healing, and well-being. This is relevant in acute pain settings given that chronic opioid users die within approximately 2.5 years of being prescribed their first opioid medication to treat acute pain. Namely, analgesic effects can also occur without formal conditioning and direct prior experience because crucial information necessary to build up expectations of analgesia can be acquired through observation of a therapeutic benefit in others. Placebo analgesic effects following the observation of a benefit in another person are similar in magnitude to those induced by directly experiencing an analgesic benefit. These observations emphasize that contextual cues substantially modulate the individual placebo analgesic effects. In this project, we propose a compelling research agenda to explore the neural mechanisms of hypoalgesia driven by observation as a foundation for future development of novel nonpharmacological pain therapies using pharmacological functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and combined EEG/fMRI. It builds on a decade of experience in placebo research in PI Colloca’s lab and with University of Maryland collaborators experienced in brain mapping and pain research. In Aim 1, we will determine the role of endogenous opioids on the neural mechanisms of observationally-induced hypoalgesia by using the opioid antagonist naloxone in a functional Magnetic Resonance Imaging (fMRI) setting. In Aim 2, we will identify the impact of empathy by exploring how being in the immersive environment can enhance observationally-induced analgesia. In Aim 3, we leverage the EEG/fMRI to determine the neural EEG/fMRI transient changes that could co-occur when socially-induced expectations are violated. The proposed research will generate mechanistic research that can be directly exploited to develop easily implementable therapeutic strategies such video clips and virtual reality tools for acute pain management.

项目概要 至少两个世纪以来，安慰剂效应在医疗保健领域一直处于矛盾的地位。 传统上用作临床试验中的对照以纠正偏差，安慰剂反应被视为一种 另一方面，要分离并准确测量治疗的效果。 另一方面，有科学证据表明安慰剂效应代表着令人着迷的心理神经生物学事件 涉及不同的中枢神经以及外周生理机制的贡献 影响疼痛感知和临床疼痛症状并显着调节对疼痛的反应 因此，安慰剂效应已从临床试验的挑战转变为临床试验的资源。 基于内源性机制触发减轻疼痛，这些机制可以在大脑中激活以促进 考虑到长期阿片类药物使用者，这与急性疼痛相关。 在第一次服用阿片类药物治疗急性疼痛后约 2.5 年内死亡。 也就是说，镇痛效果也可以在没有正式调节和直接先前经验的情况下发生，因为 建立镇痛期望所需的关键信息可以通过观察获得 观察到另一个人的获益后安慰剂的镇痛效果。 这些观察结果与直接体验镇痛效果所引起的程度相似。 强调情境线索在很大程度上调节个体安慰剂的镇痛效果。 在这个项目中，我们提出了一个引人注目的研究议程来探索痛觉减退的神经机制 以观察为驱动，为未来开发新型非药物疼痛疗法奠定基础 使用药理功能磁共振成像 (fMRI)、脑电图 (EEG) 和 它建立在 PI Colloca 实验室十年的安慰剂研究经验之上。 马里兰大学的合作者在大脑绘图和疼痛研究方面经验丰富，在目标 1 中，我们将。 确定内源性阿片类药物对观察性痛觉减退神经机制的作用 在目标 2 中，在功能性磁共振成像 (fMRI) 环境中使用阿片类拮抗剂纳洛酮。 我们将通过探索沉浸式环境如何增强同理心的影响 在目标 3 中，我们利用 EEG/fMRI 来确定神经 EEG/fMRI。 当社会引发的期望被违反时，可能会同时发生短暂的变化。 拟议的研究将产生可直接利用以轻松开发的机制研究 可实施的治疗策略，例如用于急性疼痛管理的视频剪辑和虚拟现实工具。