Brain Mechanisms Underlying CBT-Related Reductions in Fibromyalgia

描述(申请人提供)：慢性疼痛是一个普遍的国际健康问题，每年造成超过6000亿美元的成本。这项应用侧重于纤维肌痛(FM)，它的特征是持续的、广泛的身体疼痛，有明显的大脑功能改变的证据。认知行为疗法(CBT)是为数不多的有效治疗FM的方法之一，它已被证明可以减少疼痛强度和疼痛相关残疾，可能是通过减少灾难，这是一个重要的心理社会因素，在形成疼痛相关结果的个体差异方面发挥了关键作用。很可能是 大脑机制支持FM中减少灾难和减轻疼痛的有益效果，CBT在灾难中产生的减少可能会使功能失调的中枢神经系统疼痛处理“正常化”。我们之前对FM患者的研究证实，灾难发生率高的患者在处理疼痛情绪方面的大脑区域(如前脑岛和内侧丘脑)显示出与疼痛相关的激活增强。此外，灾害化与丘脑、前脑岛和默认模式网络(DMN)结构(如内侧前额叶皮质)之间的疼痛诱发功能连接改变有关。DMN是调节自我聚焦认知加工的脑区星座；我们先前的工作表明，DMN和脑岛之间的静息状态功能连接改变是FM临床疼痛的生物标志物。在我们的初步研究中，FM患者的一部分被随机分配到CBT或积极的教育控制条件下。我们发现，CBT减少了灾难，并在大脑激活和DMN连接方面产生了相应的变化。在目前的提案中，我们假设CBT产生的疼痛改善将是预期的，并通过减少灾难及其对与疼痛相关的大脑功能的影响而实现。患有FM的参与者将被随机分成8组，每周接受CBT或教育/注意力对照治疗，并进行6个月的随访。功能磁共振数据，包括静息和诱发的深层组织疼痛状态下的功能连接，将是 在基线、治疗中期和最终治疗访问后收集。我们假设CBT将减少治疗早期的灾难，导致大脑对外部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DMN和疼痛相关脑区的静息状态连通性随后的变化，这将为临床疼痛的长期改善奠定基础。我们的首要目标是了解CBT和减少灾变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，在早期治疗中识别潜在的无反应者，并促进加强对慢性肌肉骨骼疼痛的心理社会干预。

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.