Napadow Vitaly, Kim Jieun, Clauw Daniel J, Harris Richard E
Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Arthritis Rheum. 2012 Jul;64(7):2398-403. doi: 10.1002/art.34412.
A major impediment to the development of novel treatment strategies for fibromyalgia (FM) is the lack of an objective marker that reflects spontaneously reported clinical pain in patients with FM. Studies of resting-state intrinsic brain connectivity in FM have demonstrated increased insular connectivity to the default mode network (DMN), a network whose activity is increased during nontask states. Moreover, increased insular connectivity to the DMN was associated with increased spontaneous pain levels. However, as these analyses were cross-sectional in nature, they provided no insight into dynamic changes in connectivity or their relationship to variations in self-reported clinical pain. The purpose of this study was to evaluate longitudinal changes in the intrinsic brain connectivity of FM patients treated with nonpharmacologic interventions known to modulate pain levels in this patient population, and to test the hypothesis that the reduction of DMN-insula connectivity following therapy would correlate with diminished pain.
Seventeen FM patients underwent resting-state functional magnetic resonance imaging at baseline and following 4 weeks of a nonpharmacologic intervention to diminish pain. Intrinsic DMN connectivity was evaluated using probabilistic independent components analysis. Longitudinal changes in intrinsic DMN connectivity were evaluated by paired analysis, and correlations between longitudinal changes in clinical pain and changes in intrinsic DMN connectivity were investigated by multiple linear regression analysis. Changes in clinical pain were assessed with the short form of the McGill Pain Questionnaire (SF-MPQ).
Clinical pain as assessed using the sensory scale of the SF-MPQ was reduced following therapy (P=0.02). Intrinsic DMN connectivity to the insula was reduced, and this reduction correlated with reductions in pain (corrected P<0.05).
Our findings suggest that intrinsic brain connectivity can be used as a candidate objective marker that reflects changes in spontaneous chronic pain within individual FM patients. We propose that intrinsic connectivity measures could potentially be used in either research or clinical settings as a complementary, more objective outcome measure for use in FM.
纤维肌痛（FM）新型治疗策略发展的一个主要障碍是缺乏能够反映FM患者自发报告的临床疼痛的客观标志物。对FM患者静息态脑内固有连接性的研究表明，脑岛与默认模式网络（DMN）之间的连接性增加，DMN在非任务状态下活动增强。此外，脑岛与DMN之间连接性的增加与自发疼痛水平的升高相关。然而，由于这些分析本质上是横断面的，它们没有深入了解连接性的动态变化或其与自我报告的临床疼痛变化之间的关系。本研究的目的是评估接受已知可调节该患者群体疼痛水平的非药物干预治疗的FM患者脑内固有连接性的纵向变化，并检验治疗后DMN-脑岛连接性降低与疼痛减轻相关的假设。
17例FM患者在基线时以及接受为期4周的减轻疼痛的非药物干预后，接受静息态功能磁共振成像检查。使用概率独立成分分析评估固有DMN连接性。通过配对分析评估固有DMN连接性的纵向变化，并通过多元线性回归分析研究临床疼痛的纵向变化与固有DMN连接性变化之间的相关性。使用麦吉尔疼痛问卷简表（SF-MPQ）评估临床疼痛的变化。
治疗后，使用SF-MPQ感觉量表评估的临床疼痛减轻（P=0.02）。DMN与脑岛之间的固有连接性降低，且这种降低与疼痛减轻相关（校正P<0.05）。
我们的研究结果表明，脑内固有连接性可作为反映个体FM患者自发慢性疼痛变化的候选客观标志物。我们提出，固有连接性测量有可能在研究或临床环境中用作FM的补充性、更客观的结局测量指标。
