Neural Mechanisms of Immersive Virtual Reality in Chronic Pain

摘要 新冠肺炎大流行及其对阿片类药物危机的影响创造了对远程医疗和 考虑使用非药理学、低成本的干预措施作为疼痛控制武器库中的辅助药物。 我们提出了一个研究沉浸式虚拟减少疼痛的神经机制的项目 现实(VR)。VR包括通过使用实时渲染来沉浸在人工环境中 技术和最新一代的设备。我们最近证明了VR增强了疼痛耐受性 限制和迷走活动，同时改善个体疼痛、不愉快、情绪和情境 焦虑。为了增强这个项目的可译性，我们将直接深入到VR的神经机制 慢性疼痛受试者患有颞下颌关节紊乱病(S)(TMD)，该人群与 她的合作者取得了丰硕的成果。首要目标是研究疼痛的调制。 VR引起痛觉减退的机制：1)内源性MU阿片类物质的参与； 2)对急性VR的反应与长期疼痛相关结果之间的关系，以及3) 与3周VR相关的皮质兴奋性的变化。我们将使用三种主要方法：1)药理学 拮抗者方法，2)用于跟踪疼痛结果动态的生态瞬时评估(EMA) 超过6个月；以及3)高分辨率脑电图术以测量阿尔法峰值的同步性 频率(PAF)。我们将把VR诱导的痛觉减退的机制从安慰剂效应中分离出来 具有不同残疾和TMD等级的参与者。我们预计，类似于安慰剂效果的虚拟现实将 通过内源性阿片系统的参与来减少疼痛，2)VR诱导的疼痛调制能力 将导致更好的长期疼痛结果，3)3)3周的VR将有利于PAF振荡的同步 与个人虚拟现实治疗的好处相平行。该项目将结合药理学、EMA和 在TMD患者中使用脑电技术，以最大限度地提高TMD的翻译价值 由此产生的知识。该团队拥有成功协作的历史和专业知识，以产生创新的、 相关的、及时的调查结果。这项研究的成功完成将产生以机械为基础的 基于VR的干预措施的潜在应用的证据表明，这种干预可能使TMD患者获得新的、 可获得的、负担得起的治疗解决方案。

Summary The COVID-19 pandemic and its effect on the opioid crisis have created a pressing need for telemedicine and consideration for use of non-pharmacological, low cost interventions as adjuvants in pain management arsenal. We propose a project investigating neural mechanisms underlying pain reduction induced by immersive Virtual Reality (VR). VR consists of immersion in artificial environments through the use of real-time rendering technologies and latest generation devices. We have recently demonstrated that VR increases pain tolerance limits and vagal activity with a parallel improvement in individual pain unpleasantness, mood, and situational anxiety. To enhance the translatability of this project, we will directly dive into the neural mechanisms of VR in chronic pain participants suffering from Temporomandibular Disorder(s) (TMD), a population with which the PI and her collaborators have had fruitful results. The overarching goal is to investigate the pain modulation mechanisms underlying VR-induced hypoalgesia by determining 1) the involvement of endogenous mu opioids, 2) the relationship between responsiveness to acute VR and long-term pain-related outcomes, and 3) the changes in cortical excitability related to 3-week VR. We will use three main approaches: 1) a pharmacological antagonist approach, 2) An ecological momentary assessment (EMA) for tracking dynamics of pain outcomes over 6 months; and 3) a high-resolution electroencephalography to measure synchronization of peak alpha frequency (PAF). We will disentangle the mechanisms of VR-induced hypoalgesia from placebo effects among participants with distinct disabilities and grades of TMD. We expect that 1) VR, similar to placebo effects, will reduce pain through the engagement of endogenous opioid systems, 2) VR-induced pain modulation capability will result in better long-term pain outcomes, and 3) 3-week VR will favor a synchronization of PAF oscillations paralleled by individual VR therapeutic benefits. This project will combine pharmacologic, the EMA, and electroencephalographic techniques employed within TMD patients to maximize the translational value of the resulting knowledge. The team has a history of successful collaboration and the expertise to generate innovative, relevant, and timely findings. The successful completion of this research will generate mechanistic-based evidence for the potential application of VR-based interventions which might empower TMD patients with new, accessible, and affordable therapeutic solutions.