Neural Processes Underlying Pain Perception in Depression

描述（由申请人提供）：疼痛和抑郁是常见的，经常发生在同一患者身上。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。此外，疼痛和抑郁症之间的共病显着有助于较差的结果和治疗费用增加。这就提出了一个关键问题：“为什么人们在抑郁时会经历更多的痛苦？令人惊讶的是，很少有人知道疼痛和抑郁症之间的相互作用的病理生理学。这项探索性拨款提案的目标是将这些研究领域结合在一起，以解决这个问题：“抑郁和疼痛是否有共同的神经基础？”“我们建议使用功能性磁共振成像（fMRI）与当前重度抑郁症（MDD）患者以及健康对照受试者的实验疼痛范例。我们将研究行为和大脑活动的基础预期和处理厌恶性疼痛刺激。我们将使用通过脊髓丘脑通路处理的疼痛刺激来检查自上而下的疼痛调制的完整性，并假设MDD受试者的前扣带回和前扣带回的激活改变反映了内感受的改变，即整个身体的生理状况。本建议的具体目的是：1）评估目前患有MDD的受试者对疼痛的感觉和情感反应。2)确定哪些神经基质是预测和处理疼痛刺激的基础，以及简单分心对当前MDD受试者这些过程的影响。这项研究有几个重要的意义。通过测量抑郁症患者的疼痛处理改变，我们将能够：（1）量化疼痛异常处理的程度;（2）将疼痛处理与特定神经基质的激活状态联系起来;（3）提出旨在改变所提出的神经基质的大脑激活的治疗干预措施;（4）为改变的疼痛过程建立神经生物学基础;（5）为疼痛过程的改变提供神经生物学基础。以及（5）利用这些发现开发生物标志物以在未来监测治疗结果。疼痛和抑郁症是常见的，往往同时发生在同一个病人。这种并发症有助于显着较差的结果和增加的治疗成本和理解的病理生理学的疼痛抑郁症的相互作用，通过检查抑郁症患者的疼痛过程的神经生物学将阐明抑郁症如何改变一个人的反应压力。识别抑郁个体对压力的异常反应的机制可以识别预测症状形成的神经基质，并可能作为未来治疗干预的生物标志物。

DESCRIPTION (provided by applicant): Pain and depression are common and often occur in the same patient. Over 75% of patients with depression suffer from pain symptoms and between 30-60% of pain patients report significant depressive symptoms. Moreover, the comorbidity between pain and depression contributes significantly to poorer outcomes and increased cost of treatment. This raises the key question: "why people experience more pain when they are depressed? Surprisingly, little is known about the pathophysiology of the interaction between pain and depression. The goal of this exploratory grant proposal is to bring these areas of research together to address the question, "do depression and pain share common neural substrates?" We propose to use Functional Magnetic Resonance Imaging (fMRI) with an experimental pain paradigm in individuals with current Major Depressive Disorder (MDD), as well as healthy comparison subjects. We will examine behavior and brain activity underlying anticipation and processing of aversive painful stimulus. We will use pain stimuli, which are processed via the spinothalamic pathway, to examine the integrity of the top-down pain modulation and hypothesize that altered activation of insula and anterior cingulate in subjects with MDD reflects altered interoception, i.e. the physiological condition of the entire body. The specific aims of this proposal are: 1) To assess sensory and affective responses to pain in subjects with current MDD. 2) To determine which neural substrates underlie anticipation and processing of painful stimulus, as well as the effects of simple distraction on these processes in subjects with current MDD. There are several important implications of this research. By measuring altered pain processing in depressed individuals, we will be able to (1) quantify the degree to which pain is abnormally processed; (2) link pain processing to the activation status of specific neural substrates; (3) suggest treatment interventions that are aimed to altered the brain activation of the proposed neural substrates; (4) develop a neurobiological basis for altered pain processes; and (5) utilize these findings for the development of biomarkers to monitor treatment outcomes in the future. Pain and depression are common and often co-occur in the same patient. This co-morbidity contributes significantly to poorer outcomes and increased cost of treatment and understanding the pathophysiology of pain-depression interaction by examining the neurobiology of pain processes in patients with depression will elucidate how depression alters one's reaction to stress. Identifying the mechanism of the aberrant response to stress in depressed individuals may identify neural substrates that predict symptom formation and can potentially serve as biomarkers for future therapeutic intervention.