Brain Mechanisms Underlying CBT-Related Reductions in Fibromyalgia

慢性疼痛是一种普遍的国际健康问题，每年造成的费用超过6000亿美元。这种应用程序的重点是纤维肌痛（FM），其特征是持续的，广泛的身体疼痛，有明显的证据表明大脑功能改变。FM的少数有效治疗方法之一是认知行为疗法（CBT），已显示其可能通过减少灾难化来降低疼痛强度和疼痛相关残疾，灾难化是一种重要的心理社会因素，在形成疼痛相关结果的个体差异中起着至关重要的作用。很可能 脑机制支持FM中降低的灾难化和减少的疼痛的有益效果，并且CBT产生的灾难化的减少可以起到使功能失调的中枢神经系统疼痛处理“正常化”的作用。我们之前对FM患者的研究证实，灾难化程度高的患者在处理疼痛情绪方面的大脑区域显示出增强的疼痛相关激活（例如，前丘脑和内侧丘脑）。此外，灾难化与丘脑、前额叶和默认模式网络（DMN）结构（如内侧前额叶皮层）之间疼痛诱发功能连接的改变有关。DMN是介导自我聚焦认知处理的大脑区域的星座;我们先前的工作已经涉及DMN和DMN之间改变的静息状态功能连接作为FM中临床疼痛的生物标志物。在我们的初步研究中，FM患者的一个子集被随机分配到CBT或积极的教育控制条件。我们发现CBT减少了灾难化，并在大脑激活和DMN连接方面产生了相应的变化。在本提案中，我们假设CBT产生的疼痛改善将被预期和介导的灾难化及其对疼痛相关脑功能的相关影响的减少。FM受试者将随机接受8次CBT或教育/注意力控制治疗，每周一次，并随访6个月。功能性磁共振成像数据，包括静息和诱发深部组织疼痛状态下的功能连接， 在基线、治疗中期和最终治疗访视后采集。我们假设CBT将减少治疗早期的灾难化，导致大脑对外部施加的有害刺激的反应发生适应性变化。然后，这些变化将预测患者在DMN和疼痛相关脑区域中的静息状态连接的后续变化，这将成为临床疼痛长期改善的基础。我们的总体目标是了解CBT和减少灾难化促进慢性疼痛改善的神经生物学途径;这些信息将有助于完善疼痛的生物心理社会模型，在治疗早期识别潜在的无应答者，并促进慢性肌肉骨骼疼痛的心理社会干预的增强。

DESCRIPTION (provided by applicant): Chronic pain is a widespread international health problem that imposes costs of over 600 billion dollars per year. This application focuses on fibromyalgia (FM), which is characterized by persistent, widespread body pain, with significant evidence of altered brain function. One of the few effective treatments for FM is cognitive-behavioral therapy (CBT), which has been shown to reduce pain intensity and pain-related disability, potentially via reductions in catastrophizing, an important psychosocial factor that plays a crucial role in shaping individual differences in pain- related outcomes. It is likely that brain mechanisms underpin the beneficial effects of lowered catastrophizing and reduced pain in FM, and CBT-produced decrements in catastrophizing may act to "normalize" dysfunctional central nervous system pain processing. Our previous study in FM patients confirms that patients who are high in catastrophizing show enhanced pain-related activation in brain areas that process emotional aspects of pain (e.g., anterior insula and medial thalamus). In addition, catastrophizing was associated with altered pain-evoked functional connectivity between thalamus, anterior insula, and default mode network (DMN) structures such as medial prefrontal cortex. The DMN is a constellation of brain regions that mediate self- focused cognitive processing; our prior work has implicated altered resting-state functional connectivity between DMN and insula as a biomarker for clinical pain in FM. In our pilot study, a subset of FM patients was randomized to CBT or an active educational control condition. We found that CBT reduced catastrophizing and produced corresponding changes in brain activation and DMN connectivity. In the present proposal, we hypothesize that CBT-produced improvements in pain will be anticipated and mediated by reductions in catastrophizing and their associated effects on pain-related brain functioning. Participants with FM will be randomized to 8 weekly treatments with CBT or an education/attention control, and followed up for 6 months. Functional MRI data, including functional connectivity during both a resting and evoked deep- tissue pain state, will be collected at baseline, mid-treatment, and after the final treatment visit. We hypothesize that CBT will reduce catastrophizing early in treatment, resulting in adaptive changes in the brain's responses to an externally-applied noxious stimulus. These changes will then predict subsequent changes in patients' resting state connectivity in DMN and pain- relevant brain regions, which will underlie long-term improvements in clinical pain. Our overarching goal is to understand the neurobiological pathways by which CBT and reduced catastrophizing facilitate improvements in chronic pain; such information will help to refine biopsychosocial models of pain, identify potential non-responders early in treatment, and facilitate the enhancement of psychosocial interventions for chronic musculoskeletal pain.