Brain Mechanisms Underlying CBT-Related Reductions in Fibromyalgia

摘要 慢性疼痛是一个普遍的国际健康问题，造成超过6000亿美元的费用 美元每年。该应用程序的重点是纤维肌痛（FM），其特征在于 持续的，广泛的身体疼痛，有明显的证据表明大脑功能改变。之一 FM的一些有效治疗方法是认知行为疗法（CBT），已被证明 减少疼痛强度和疼痛相关的残疾，可能通过减少灾难性， 一个重要的心理社会因素，在形成个体疼痛差异方面起着至关重要的作用- 相关成果。这可能是大脑机制的基础上的有益影响，降低 灾难化和减少疼痛的FM，和CBT产生的递减灾难化可能 作用于“正常化”功能失调的中枢神经系统疼痛处理。我们以前的研究， FM患者证实，灾难化程度高的患者表现出增强的疼痛相关性， 处理疼痛的情感方面的大脑区域的激活（例如，前内侧 丘脑）。此外，灾难化与疼痛诱发功能的改变有关。 丘脑、前丘脑和默认模式网络（DMN）结构之间的连接 例如内侧前额叶皮层。DMN是一组大脑区域， 集中的认知处理;我们先前的工作涉及改变静息状态功能 DMN和DMN之间的连接作为FM中临床疼痛的生物标志物。在我们的试点研究中， FM患者的子集被随机分配到CBT或积极的教育控制条件。我们 发现CBT减少了灾难化，并在大脑中产生了相应的变化， 激活和DMN连接。在本提案中，我们假设CBT产生的 疼痛的改善将通过减少灾难化及其 对疼痛相关大脑功能的影响。FM受试者将随机分配至 每周8次CBT或教育/注意力控制治疗，并随访6个月。 功能性MRI数据，包括静息和诱发深- 将在基线、治疗中期和最终治疗访视后收集组织疼痛状态。 我们假设，CBT将减少治疗早期的灾难化，从而产生适应性的 大脑对外部有害刺激的反应变化。这些变化将 然后预测患者在DMN和疼痛中的静息状态连接的后续变化- 相关的大脑区域，这将成为临床疼痛长期改善的基础。我们 总体目标是了解CBT和减少CBT的神经生物学途径。 灾难化有助于改善慢性疼痛;这些信息将有助于改善 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， 促进加强对慢性肌肉骨骼疼痛的心理社会干预。

ABSTRACT 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.