Identifying Virtual Reality Analgesia Mechanisms by Pharmacologic Manipulation

6.项目总结/摘要 本提案涉及PA-07 - 282（机制、模型、测量， 和疼痛研究管理），并专门针对生物行为疼痛，疼痛， 管理和翻译疼痛研究。我们提出了一系列的研究，在实验室疼痛设置 （健康志愿者的热和/或电疼痛），旨在测试三个特定和相关的假设 探索神经生理机制，沉浸式虚拟现实（VR）作为一种非 药物疼痛管理技术。VR镇痛的同时药物操作 这些研究可能会产生机制的见解，将改善未来的临床应用的VR曝光， 让沉浸式VR成为更多患者更有效的镇痛工具。VR的理想临床应用将 可能作为"多模式镇痛"方案的一个组成部分，与以下药物联合给药： 药物镇痛剂。然而，这些药物的累加和潜在协同镇痛作用是不可能的。 技术还有待研究。该提案侧重于同时使用VR曝光， 已知影响疼痛感知的全身性镇痛激动剂或拮抗剂，并建立在先前的工作基础上， 我们的研究小组比较了同时进行的主观和神经影像学证据的镇痛与沉浸式 VR和全身阿片类药物治疗。该建议有两个广泛的目标：（1）测试特定的假设， VR镇痛的神经生理学机制，同时使用主观和功能脑成像 （2）确定潜在的添加剂和/或协同作用， 联合沉浸式VR和药物镇痛给药的镇痛效果。这些目标将是 通过三个具体目的：（1）确定VR的主观镇痛效果的程度 阿片受体拮抗剂纳洛酮可抑制（或不抑制）镇痛作用;（2）确定阿片受体拮抗剂纳洛酮对镇痛作用的影响。 沉浸式VR和N-甲基-D-天冬氨酸（NMDA）拮抗作用的比较和累加效应， 剂量氯胺酮（亚麻醉剂量，无致幻作用，但与镇痛相关， （3）确定沉浸式VR的比较效果， 低剂量氯胺酮对大鼠标准脑区疼痛相关脑活动的NMDA拮抗作用 “疼痛矩阵”，以及与疼痛体验的调制相关的大脑结构，以及 将观察到的大脑活动与疼痛体验的主观报告相关联。资料来自 建议的研究将指导（1）未来的研究，确定具体的镇痛机制沉浸 VR，（2）在“多模式”中VR暴露和药理学镇痛药的深思熟虑的临床组合 镇痛"的方法，以减少程序疼痛，（3）未来的评估，成本效益的应用 VR系统旨在最大限度地提高沉浸式VR在各种临床疼痛环境中的镇痛效果。

6. Project Summary/Abstract This proposal addresses the research objectives identified in PA-07-282 (Mechanisms, Models, Measurement, and Management in Pain Research) and specifically targets the topics of Biobehavioral Pain, Pain Management, and Translational Pain Research. We propose a series of studies in the laboratory pain setting (thermal and/or electrical pain in healthy volunteers) designed to test three specific and related hypotheses exploring the neurophysiologic mechanisms that underlie immersive Virtual Reality (VR) as a non- pharmacologic pain management technique. The concurrent pharmacologic manipulation of VR analgesia in these studies will likely yield mechanistic insights that will improve future clinical application of VR exposure, and make immersive VR a more effective analgesic tool for more patients. The ideal clinical use of VR will likely be as one component of a "multimodal analgesia" regimen, administered in combination with pharmacologic analgesics. However, the additive and potential synergistic analgesic effects of these techniques have yet to be examined. This proposal focuses on the concomitant use of VR exposure and systemic analgesic agonists or antagonists known to affect pain perception, and builds on previous work by our group that has compared concurrent subjective and neuroimaging evidence of analgesia with immersive VR and systemic opioid therapy. This proposal has two broad goals: (1) to test specific hypotheses concerning the neurophysiologic mechanisms of VR analgesia, using concomitant subjective and functional brain imaging (fMRI) assessments of the pain experience, and (2) to determine the potential additive and/or synergistic analgesic effects of combined immersive VR and pharmacologic analgesic administration. These goals will be met through three Specific Aims: (1) To determine the extent to which subjective analgesic effects of VR analgesia are inhibited (or not) by opioid receptor antagonism with naloxone; (2) To determine the comparative and additive effects of immersive VR and N-methyl-D-aspartate (NMDA) antagonism with low- dose ketamine (at a sub-anesthetic dose devoid of hallucinatory effects, but associated with analgesia, expansive mood, and heightened perception); (3) To determine the comparative effects of immersive VR and NMDA antagonism with low-dose ketamine on pain-related brain activity in standard brain regions of the "pain matrix", as well as in brain structures associated with modulation of the pain experience, and to correlate observed brain activity with subjective reports of the pain experience. Information gained from the proposed studies will guide (1) future investigations that define specific analgesic mechanisms of immersive VR, (2) the thoughtful clinical combination of VR exposure and pharmacologic analgesics in a "multimodal analgesia" approach to reducing procedural pain, and (3) future assessments of the cost-effective application of VR systems designed to maximize the analgesic effect of immersive VR in various clinical pain settings.