Neural Processes Underlying Pain Perception in Depression

描述(申请人提供)：疼痛和抑郁是常见的，通常发生在同一个患者。超过75%的抑郁症患者有疼痛症状，30%-60%的疼痛患者报告有明显的抑郁症状。此外，疼痛和抑郁之间的共病显著导致更差的结果和更高的治疗成本。这就引出了一个关键问题：“为什么人们在抑郁时会经历更多的痛苦？令人惊讶的是，人们对疼痛和抑郁之间相互作用的病理生理学知之甚少。这项探索性拨款提案的目标是将这些研究领域聚集在一起，解决这样一个问题：“抑郁症和疼痛有共同的神经基础吗？”我们建议在目前患有严重抑郁障碍(MDD)的个体以及健康对照对象中使用功能磁共振成像(FMRI)和实验性疼痛范式。我们将检查行为和大脑活动潜在的预期和处理厌恶痛苦的刺激。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疼痛调制的完整性，并假设MDD受试者脑岛和前扣带核的激活改变反映了内部感觉的改变，即整个身体的生理状况。这项建议的具体目标是：1)评估患有当前MDD的受试者对疼痛的感觉和情感反应。2)确定目前患有MDD的受试者对痛苦刺激的预期和加工所依据的神经基质，以及简单的分心对这些过程的影响。这项研究有几个重要的启示。通过测量抑郁症患者疼痛过程的改变，我们将能够(1)量化疼痛被异常处理的程度；(2)将疼痛处理与特定神经底物的激活状态联系起来；(3)提出旨在改变拟议神经底物的大脑激活的治疗干预建议；(4)为改变疼痛过程建立神经生物学基础；以及(5)利用这些发现开发生物标记物来监测未来的治疗结果。疼痛和抑郁是常见的，而且通常在同一患者中同时发生。这种共病显著地导致了较差的结果和治疗成本的增加，通过检测抑郁症患者疼痛过程的神经生物学来了解疼痛-抑郁相互作用的病理生理学，将有助于阐明抑郁症如何改变一个人对压力的反应。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底物，并可能作为未来治疗干预的生物标记物。

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.