Neural correlates of hypoalgesia driven by observation

项目摘要 安慰剂效应在至少两个世纪的医疗保健中占据着矛盾的位置。一方面，安慰剂 传统上被用作临床试验的对照，以纠正偏倚，安慰剂反应被视为 为了隔离和准确测量治疗的效果，需要将影响因素排除在外。另 另一方面，有科学证据表明，安慰剂效应代表了迷人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，并显著调节对疼痛的反应 治疗学因此，安慰剂效应已经从临床试验的挑战转变为 触发基于内源性机制的疼痛减轻，该机制可以在大脑中激活以促进 记忆力减退，自我修复和健康。这与急性疼痛环境有关，因为慢性阿片类药物使用者 在首次使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条件反射和直接先前经验的情况下发生， 建立镇痛预期所需的关键信息可以通过观察 对其他人的治疗效果。在另一个人中观察到获益后的安慰剂镇痛作用 与直接体验镇痛益处所诱导的程度相似。这些观察结果 强调上下文线索实质上调节个体安慰剂镇痛效果。 在这个项目中，我们提出了一个引人注目的研究议程，以探索痛觉减退的神经机制 由观察驱动，作为未来开发新型非药物疼痛疗法的基础 使用药理学功能磁共振成像（fMRI），脑电图（EEG）， 结合脑电图和功能磁共振成像它建立在PI Colloca实验室十年安慰剂研究的经验基础上， 马里兰州大学的合作者在脑图谱和疼痛研究方面经验丰富。在目标1中，我们 确定内源性阿片类物质对观察诱导的痛觉减退的神经机制的作用 通过在功能性磁共振成像（fMRI）中使用阿片类拮抗剂纳洛酮。在目标2中， 我们将通过探索沉浸式环境如何增强 观察诱导镇痛。在目标3中，我们利用EEG/fMRI来确定神经EEG/fMRI， 当社会诱导的期望被违反时，可能会同时发生的短暂变化。 拟议的研究将产生机制的研究，可以直接利用开发容易 可实施的治疗策略，如用于急性疼痛管理的视频剪辑和虚拟现实工具。

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.