Brain Imaging and Pain: Analysis of Placebo Analgesia

慢性疼痛是一个重要的公共卫生问题，影响超过1亿成年人， 每年超过六千亿美元。目前对慢性疼痛的治疗缺乏 有效性和阿片类药物治疗导致了显着的滥用，成瘾，和二次公众 健康危机。我们已经表明，内源性疼痛调制，在“安慰剂”的形式， 推拿现在有一个明确的神经基础，提示下行疼痛 在大脑内部或从大脑到低级神经系统的调节。我们的工作已经确定了 安慰剂作为慢性疼痛患者潜在可接受的干预措施， 来加强现有的治疗，或者作为一种独立的治疗。迄今为止 脊髓机制对安慰剂镇痛的作用在很大程度上是推测性的。我们 建议调查关于大脑和脊髓机制的具体假设， 通过使用功能性磁刺激， 磁共振成像（FMRI）。脊髓的神经成像是一种创新的新的 迄今为止，这种方法对于安慰剂机制的研究是不可行的。我们将联合收割机 这种新方法与我们以前发表的，以及明确的安慰剂操作， 实验设计，使我们能够调查大脑和脊髓的相对贡献， 安慰剂镇痛的机制。我们将使用传统的功能磁共振成像，以及功能 连通性分析，以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，将允许调查更多的中枢依赖性机制，与那些 更依赖于周围神经系统。我们的调查小组有所有必要的 在慢性疼痛，疼痛处理，定量感觉测试，神经成像，和 实验设计，以成功地实现本申请中提出的目标。我们有 反复展示了我们成功招募参与者的能力， 成功地采用了所有的程序，无论是在同行评审的出版物，或作为 在我们的初步研究中，我们之前工作的一个重要发现表明 安慰剂干预措施的可接受性是对 安慰剂的机制因此，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，以公众，疼痛医生，和病人将增加可接受性 他们在临床实践中，从而改善疼痛治疗。

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.