Brain Mechanisms Supporting Mindfulness Meditation-Based Chronic Pain Relief

疼痛是一种涉及感官、认知和情感因素的多维体验。这些因素之间相互作用的星座使得慢性疼痛的治疗具有挑战性，往往是一个经济负担。事实上，慢性疼痛影响着超过1亿美国人，每年给美国造成的损失约为6350亿美元。由于阿片类药物滥用和成瘾呈指数级增长，广泛使用阿片类药物治疗慢性疼痛导致了所谓的“阿片类药物流行病”。这些惊人的统计数字突出了开发、测试和验证快速、非药物治疗疼痛方法的重要性。正念冥想是一种在实验和临床环境中被发现能显著减轻疼痛的技术。然而，缺乏机制数据和广泛的冥想训练需要体验镇痛的假设限制了这种具有成本效益和无麻醉治疗的临床部署。我们实验室最近的研究结果表明，仅仅经过四次（每次20分钟）的训练，正念冥想就能显著降低疼痛强度和不愉快程度。在两项功能神经成像研究中，我们使用基于灌注的MRI（动脉自旋标记），发现正念冥想通过多种大脑机制减少疼痛，这些机制与增强认知控制、情绪调节和衰减上升的伤害性输入有关。然而，这些结果不能推广到慢性疼痛，因为它们与健康、无疼痛的参与者和热诱发的疼痛有关。重要的是，支持正念冥想调节慢性疼痛的大脑机制尚不清楚。因此，R01研究的中心目的是确定支持通过急性训练的正念冥想来调节急性加重的慢性腰痛的具体机制，这是最普遍和经济负担沉重的慢性疼痛状况。我们将确定通过正念冥想减轻实验引起的疼痛的神经机制（即OFC、sgACC、丘脑）是否也与调节慢性腰痛有关。支持以正念为基础的疼痛缓解的神经功能联系也是未知的。因此，我们还将研究基于正念的疼痛缓解是否与丘脑默认模式网络解耦有关，以提供机制见解，以更好地开发针对疼痛的干预措施。

Pain is a multidimensional experience that involves sensory, cognitive and affective factors. The constellation of interactions between these factors renders the treatment of chronic pain challenging and often a financial burden. In fact, chronic pain affects over 100 million Americans and costs the United States approximately $635 billion dollars a year. The widespread use of opioids to treat chronic pain has led to the so-called “opioid epidemic” due to the exponential growth in opioid misuse and addiction. These staggering statistics highlight the importance of developing, testing and validating fast-acting, non-pharmacological approaches to treat pain. Mindfulness meditation is a technique that has been found to significantly reduce pain in experimental and clinical settings. However, lack of mechanistic data and the assumption that extensive meditation training is required to experience analgesia has limited the clinical deployment of this cost-effective and narcotic-free treatment. Recent findings from our laboratory determined that mindfulness meditation, after only four sessions (20 minutes/session) of training, dramatically reduces pain intensity and unpleasantness ratings. Across two functional neuroimaging studies, employing perfusion-based MRI (arterial spin labeling), we found that mindfulness meditation reduces pain through multiple brain mechanisms related to increased cognitive control, emotion regulation and attenuation of ascending nociceptive input. However, these results cannot be generalized to chronic pain because they were associated with healthy, pain-free participants and thermally induced pain. Importantly, the brain mechanisms supporting the modulation of chronic pain by mindfulness meditation remain unknown. Thus, the central aim of the proposed R01 study is to determine the specific mechanisms supporting the modulation of acutely exacerbated chronic low-back pain, the most prevalent and financially burdensome chronic pain condition, by acutely trained mindfulness meditation. We will determine if the neural mechanisms found to attenuate experimentally induced pain by mindfulness meditation (i.e., OFC, sgACC, thalamus) are also associated with modulating chronic low back pain. The neurofunctional connections supporting mindfulness-based pain relief are also unknown. Thus, we will also examine if mindfulness-based pain relief is associated with thalamic-default mode network decoupling to provide mechanistic insight to better develop interventions to target pain.