Neural correlates of hypoalgesia driven by observation

项目摘要 至少两个世纪以来，安慰剂效应在医疗保健中一直处于矛盾的地位。一方面，安慰剂 传统上被用作临床试验的对照，以纠正偏见，而安慰剂反应被视为 为了隔离和准确地衡量治疗效果，需要考虑影响。另一方面 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和外周生理机制的贡献， 影响疼痛知觉和临床疼痛症状，实质上调节对疼痛的反应 治疗学。因此，安慰剂效应已经从临床试验的挑战转变为 根据内源性机制触发疼痛减轻，这可以在大脑中激活以促进 心智不全、自我修复和幸福。这在急性疼痛环境中是相关的，因为慢性阿片类药物使用者 在开出第一个治疗急性疼痛的阿片类药物后大约2.5年内死亡。 也就是说，止痛效果也可以在没有正式的条件反射和直接的事先经验的情况下发生，因为 建立对止痛的期望所需的关键信息可以通过观察 对其他人的治疗益处。观察到另一人受益后的安慰剂止痛效果 在大小上与直接体验止痛益处所引起的症状相似。这些观察结果 强调背景线索实质上调节了个体的安慰剂止痛效果。 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。 由观察驱动，作为未来开发新的非药物止痛疗法的基础 使用药理功能磁共振成像(FMRI)、脑电(EEG)和 脑电/功能磁共振联合检查。它建立在皮科洛卡实验室十年的安慰剂研究经验基础上，并与 马里兰大学的合作者在脑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在观察性痛觉减退的神经机制中的作用 通过在功能磁共振成像(FMRI)设置中使用阿片拮抗剂纳洛酮。在目标2中， 我们将通过探索身临其境的环境如何提高同理心的影响来确定 观察性诱导止痛。在目标3中，我们利用EEG/fMRI来确定神经EEG/fMRI 当违反社会诱导的期望时，可能会同时发生的短暂变化。 拟议的研究将产生可以直接利用的机械性研究，以便容易地开发 可实施的治疗策略，如视频剪辑和用于急性疼痛管理的虚拟现实工具。

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.