Brain Mechanisms Supporting Mindfulness-Based Pain Relief

描述（由申请人提供）：疼痛是一种涉及感官、认知和情感因素的多维体验，使临床疼痛的治疗具有挑战性，通常是一种经济负担。正念冥想已经在实验和临床环境中被证明可以减轻疼痛，同时也具有成本效益。然而，正念冥想的疼痛缓解机制仍然缺乏特征。K99/R00申请的中心研究目的是确定与正念疼痛缓解相关的行为、神经和药理学机制。为了实现这一目标，扎伊丹博士将采用广泛的方法来解开正念冥想的潜在镇痛特性。首先，冥想的缓和作用可能只是反映了与一个人正在冥想的信念相关的需求特征。为了解决这个问题，扎伊丹博士开发并采用了假正念冥想干预来测试正念冥想激活高阶大脑区域[吻侧前扣带皮层（ACC）]的假设，与假正念冥想相比，可以减轻疼痛。相反，与正念冥想相比，假冥想被认为是通过激活与安慰剂镇痛相关的大脑区域（背外侧前额皮质）来减轻疼痛。有趣的是，冥想相关的疼痛缓解涉及含有高浓度阿片受体的大脑区域（ACC，前岛）。然而，目前尚不清楚冥想相关的疼痛缓解是否由内源性阿片能系统介导。在冥想和热刺激期间服用阿片拮抗剂可以显著降低冥想的镇痛效果。此外，与冥想减轻疼痛相关的特定神经功能联系仍然未知。扎伊丹博士将利用神经成像和功能连通性分析来验证冥想会激活参与认知重新评估过程（ACC）的神经系统，从而减少与疼痛相关的大脑活动的假设。从这些研究活动中获得的知识将为正念冥想的疗效和镇痛特性提供新的机制见解，这是临床疼痛治疗的重要考虑因素。这个K99/R00应用程序的培训目标是获得神经成像和药理学方法方面的额外经验，使扎伊丹博士能够成功地过渡到专注于识别正念冥想的特定镇痛特性的独立职业。培训计划包括个人和团队指导策略、神经科学、药理学技术、统计学、科学验证的冥想训练和职业发展方面的额外课程。Zeidan博士得到了他的导师和职业发展咨询委员会的大力支持，该委员会由各自领域的顶尖专家组成。K99/R00奖的培训和研究活动将为扎伊丹博士提供资源、知识基础和技能，以建立一个关于正念和疼痛机制的独立项目研究线。

DESCRIPTION (provided by applicant): Pain is a multidimensional experience that involves sensory, cognitive and affective factors that make the treatment of clinical pain challenging and often a financial burden. Mindfulness meditation has been shown to alleviate pain in experimental and clinical settings, and at the same time is cost-effective. However, the pain- relieving mechanisms of mindfulness meditation remain poorly characterized. The central research aim of the proposed K99/R00 application is to identify the behavioral, neural, and pharmacologic mechanisms associated with mindfulness-based pain relief. To accomplish this aim, Dr. Zeidan will employ a wide-ranging approach to disentangle the potential analgesic properties of mindfulness meditation. For one, meditation's palliative effects may simply reflect demand characteristics associated with the belief that one is meditating. To address this issue, Dr. Zeidan has developed and employed a sham mindfulness meditation intervention to test the hypothesis that mindfulness meditation activates higher-order brain regions [rostral anterior cingulate cortex (ACC)] to reduce pain when compared to sham mindfulness meditation. In contrast, sham meditation is postulated to reduce pain by activating brain regions associated with placebo-analgesia (dorsolateral prefrontal cortex) when compared to mindfulness meditation. Interestingly, meditation-related pain relief engages brain regions (ACC, anterior insula) containing a high concentration of opioid receptors. However, it is still unknown if meditation-related pain relief is mediated by endogenous opioidergic systems. Administration of an opioid antagonist during meditation and noxious heat stimulation is hypothesized to significantly reduce the pain- relieving effects of meditation. In addition, the specific neuro-functional connections associated with reducing pain by meditation remain unknown. Dr. Zeidan will employ neuroimaging and functional connectivity analyses to test the hypothesis that meditation will activate neural systems involved in cognitive reappraisal processes (ACC) to reduce pain-related brain activity. The knowledge to be gained from these research activities will provide novel mechanistic insight into the efficacy and analgesic properties associated with mindfulness meditation, an important consideration for the treatment of clinical pain. The training goal of this K99/R00 application is to gain additional experience in neuroimaging and pharmacologic methodologies to allow Dr. Zeidan to successfully transition to an independent career focused on identifying the specific analgesic properties of mindfulness meditation. The training plan includes individual and team-mentoring strategies, additional coursework in neuroscience, pharmacologic techniques, statistics, scientifically validated meditation training, and career development. Dr. Zeidan is strongly supported by his mentor and career development advisory committee that is composed of leading experts in their respective fields. The proposed training and research activities of this K99/R00 award will provide Dr. Zeidan with the resources, knowledge base and skills to establish an independent line of programmatic research on the mechanisms of mindfulness and pain.