The Neural Basis of Pain Modulation in Depression

描述（由申请人提供）：疼痛和抑郁是常见的，通常在同一患者中同时发生，并导致严重残疾。超过75%的抑郁症患者患有疼痛症状，30-60%的疼痛患者报告有明显的抑郁症状。重要的是，疼痛和抑郁之间的共病显著导致（1）不良结局和（2）治疗费用增加。该计划的主要目标是准备候选人发展成为疼痛和抑郁共病的神经机制专家。培训计划的目的是提高候选人在以下方面的知识：1）情绪障碍的神经生物学和临床表现; 2）识别和制定情绪障碍和疼痛领域的临床相关研究问题; 3）开发疼痛-情绪相互作用的临床驱动神经科学系统模型的能力。第二个目标是加强候选人在功能性磁共振成像（fMRI）方面的专业知识，以更好地开发范式和技术来描绘对疼痛-情绪相互作用评估至关重要的神经基质。这项研究计划旨在探讨疼痛和抑郁症之间的相互关系，解决这样一个问题：“抑郁症和疼痛有共同的神经基质吗？”“这些研究将扩大申请人目前的研究兴趣。最近的证据表明，提供自上而下的疼痛调制的神经回路的完整性在情绪障碍患者中受到损害。对于这种自上而下的调节来说，两种重要的认知/情感机制包括：（1）疼痛预期，它使大脑能够改变对疼痛强度及其情感质量的处理;（2）分心，它被自上而下的神经基质用来减弱疼痛体验。这些过程的完整性将使用功能性磁共振成像（fMRI）通过比较患有当前重度抑郁症（MOD）的个体与健康对照受试者来检查。研究计划的具体目的是：1）评估当前MOD受试者对疼痛的感觉和情感反应; 2）确定当前MOD受试者对疼痛刺激的预期背后的神经基质; 3）确定当前MDD受试者通过分心进行疼痛调制背后的神经基质。了解疼痛和抑郁的相互作用将对以下方面产生深远的影响：（1）开发抑郁症风险人群的疼痛评估;（2）开发抑郁症疼痛治疗结果的生物标志物;（3）量化情绪对疼痛过程的影响及其对治疗的敏感性。鉴于疼痛和抑郁症经常合并症，这项研究的结果可能会从根本上改变精神科医生对待抑郁症及其神经生物学基础的方式。

DESCRIPTION (provided by applicant): Pain and depression are common, often co-occur in the same patient, and result in significant disability. Over 75% of patients with depression suffer from pain symptoms and between 30-60% of pain patients report significant depressive symptoms. Importantly, the comorbidity between pain and depression contributes significantly to (1) poorer outcomes and (2) increased cost of treatment. The primary goal of this proposal is to prepare the candidate to develop into an expert in the neural mechanisms underlying the comorbidity of pain and depression. The purpose of the training plan is to enhance the candidate knowledge in: 1) neurobiology and clinical manifestation of mood disorders; 2) identification and formulation of clinically relevant research problems in the area of mood disorders and pain; 3) the ability to develop clinically driven neuroscience system models of pain-mood interactions. The secondary goal is to strengthen the candidate's expertise in functional Magnetic Resonance Imaging (fMRI) to better develop paradigms and techniques to delineate the neural substrates that are important for pain-mood interaction assessment. The research plan aims to examine the inter-relationship between pain and depression addressing the question, "do depression and pain share common neural substrates?" These studies will extend the current research interests of the applicant. Recent evidence indicates that the integrity of the neural circuits that provide top-down pain modulation is compromised in patients with mood disorders. Two cognitive/affective mechanisms that are important for this top-down modulation include: (1) Pain Anticipation, which enables the brain to alter the processing of pain intensity and its affective quality; and (2) Distraction, which is used by top-down neural substrates to attenuate the experience of pain. The integrity of these processes will be examined using Functional Magnetic Resonance Imaging (fMRI) by comparing individuals with current Major Depressive Disorder (MOD) to healthy comparison subjects. The specific aims of research plan are: 1) To assess sensory and affective responses to pain in subjects with current MOD; 2) To determine which neural substrates underlie anticipation of painful stimulus in subjects with current MOD; 3) To establish which neural substrates underlie pain modulation by distraction in subjects with current MDD. Understanding how pain and depression interaction will have profound implications for (1) the development of assessments of pain in people at risk for depression; (2) the development of biomarkers for treatment outcomes of pain in depression, (3) the quantification of the emotional effects on pain processes and their susceptibility to treatment. Given the frequent comorbidity of pain and depression, results of this study may fundamentally alter how psychiatrists approach depression and its neurobiological underpinnings.