The Neural Basis of Pain Modulation in Depression

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，疼痛和抑郁症之间的共病显着导致不良结局和治疗费用增加。申请人在K99阶段的先前工作表明，患有重度抑郁症（MDD）的受试者对实验性疼痛的情感反应增加。这种增加的情感反应与情感处理回路内的超敏反应和情感调节回路内的低敏反应相关，表明MDD通过情感上偏置其感知来影响疼痛处理，这导致无法调节疼痛体验。因此，在MDD患者中，提供自上而下疼痛调节的神经回路的完整性受到损害。对于这种自上而下的调节，有两种重要的认知/情感机制：[1]疼痛预期，它使大脑能够改变对疼痛的处理;和（2）分心，它被自上而下的神经基质用来减弱疼痛的体验。将使用功能性磁共振成像（fMRI）通过比较当前MDD患者与健康受试者来检查这些过程的完整性。 ROO应用程序的主要目标是通过检查疼痛调制的行为和神经相关性来进一步理解疼痛与抑郁的相互作用，以最终回答“为什么人们在抑郁时会感到更多疼痛？“具体目标是：1）评估MDD患者对疼痛的感觉和情感反应; 2）确定哪些神经基质是MDD患者对疼痛刺激预期的基础; 3）确定哪些神经基质是MDD患者通过分心进行疼痛调制的基础。了解疼痛和抑郁如何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

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 poorer outcomes and increased cost of treatment. Prior work of the applicant during the K99 phase showed that subjects with Major Depressive Disorder (MDD] show increased affective response to experimental pain. This increased affective response was associated with hypersensitivity within emotional processing circuitry and hyposensitivity within emotional regulation circuitry suggesting that MDD impacts pain processing by affectively biasing its perception, which leads to inability to modulate pain experience. Therefore, the integrity of the neural circuits that provide top-down pain modulation is compromised in MDD patients. 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; 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 MDD to healthy subjects. The main goal of the ROO application is to further our understanding of the painrdepression interaction by examining behavior and neural correlates of pain modulation in order to ultimately answer the question "why people feel more pain when they are depressed?" The specific aims are: 1) To assess sensory and affective responses to pain in MDD; 2) To determine which neural substrates underlie anticipation of painful stimulus in MDD; 3] To establish which neural substrates underlie pain modulation by distraction in MDD. Understanding how pain and depression interact 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 theirsusceptibility to treatment