Brain Imaging and Pain: Analysis of Placebo Analgesia

慢性疼痛是一个重大的公共卫生问题，影响着1亿多成年人， 每年占美国6000亿美元以上。目前慢性疼痛的治疗方法缺乏 疗效和阿片类药物治疗导致了严重的滥用、成瘾和继发公众 健康危机。我们已经证明了内源性疼痛调制，以“安慰剂”的形式 手法现在有一个明确的神经基础，暗示着下行疼痛 在大脑内部或从大脑到更低的神经系统的调制。我们的工作已经确定 安慰剂作为慢性疼痛患者的一种潜在可接受的干预方法 以加强现有的治疗方法，或者作为一种独立的治疗方法。到目前为止， 脊髓机制对安慰剂止痛的贡献在很大程度上是推测的。我们 建议研究关于大脑和脊髓机制的具体假说，以及 它们通过使用功能磁效应与安慰剂镇痛模型的相互作用 磁共振成像(FMRI)。脊髓的神经成像是一种创新的新技术 迄今为止，对于安慰剂机制的研究来说，这种方法是不可行的。我们将联合起来 这一新方法与我们之前发表的、阐述良好的安慰剂操作和 实验设计将使我们能够研究大脑和脊髓的相对贡献 安慰剂止痛的机制。我们将同时使用传统功能磁共振成像和功能磁共振成像 用连通性分析来研究大脑中感兴趣的先验区域之间的关系 和脊髓。我们的创新研究设计，以前只使用大脑 成像，将允许研究更中心依赖的机制，而不是那些 对周围神经系统的依赖性更强。我们的调查团队具备所有必要的条件 在慢性疼痛、疼痛处理、定量感觉测试、神经成像和 成功实现本申请中提出的目标的实验设计。我们有 反复表明我们有能力成功地为提议的设计招募参与者，以及 已成功采用所有程序，无论是在同行评议的出版物中，还是作为 我们的初步研究证明了这一点。我们之前工作中的一个关键发现表明 安慰剂干预的可接受性是对 安慰剂的作用机制。因此，除了全面了解 安慰剂的机制可能导致新的治疗方法，能够描述 这些机制对公众、疼痛从业者和患者都将增加可接受性 在临床实践中，从而提高疼痛治疗水平。

Chronic pain represents a significant public health concern, affecting over 100 million adults, and accounting for over $600 billion US annually. Current treatments for chronic pain lack efficacy, and opioid treatments have led to a significant misuse, addiction, and secondary public health crisis. We have shown that endogenous pain modulation, in the form of “placebo” manipulations have a now well-defined neural underpinning, suggestive of descending pain modulation within and perhaps from the brain to lower nervous system. Our work has identified placebo as a potentially acceptable intervention for patients with chronic pain either as a method to enhance existing treatments, or perhaps as a stand-alone treatment. To date, the contribution of spinal cord mechanisms to placebo analgesia has been largely speculative. We propose to investigate specific hypotheses about both brain and spinal cord mechanisms, and their interactions to a model of placebo analgesia through the use of functional magnetic resonance imaging (FMRI). The neural imaging of the spinal cord is an innovative new approach heretofore not feasible for the investigation of placebo mechanisms. We will combine this new approach with our previously published, and well articulated placebo manipulation and experimental design that will allow us to investigate the relative contribution of brain and cord mechanisms in placebo analgesia. We will employ both traditional fMRI, as well as functional connectivity analyses to investigate relationships among a priori regions of interest in the brain and the spinal cord. Our innovative research design, previously employed with only brain imaging, will allow for the investigation of more centrally dependent mechanisms, vs. those that are more peripheral nervous system dependent. Our team of investigators has all the necessary expertise in chronic pain, pain processing, quantitative sensory testing, neuroimaging, and experimental design to successfully accomplish the aims proposed in this application. We have repeatedly shown our ability to successfully recruit participants for the proposed design, and have successfully employed all the procedures, either in peer reviewed publications, or as demonstrated in our preliminary studies. One critical finding from our previous work has shown that the acceptability of placebo interventions is the empirical support and understanding of the mechanisms of placebo. Thus, in addition to developing a complete understanding of the mechanisms of placebo that might results in new treatment approaches, being able to describe these mechanisms to the public, pain practitioners, and to patients will increase the acceptability of them in clinical practice, thus improving pain treatment.