University of Aberdeen, Aberdeen, UK.
University of Michigan, Ann Arbor.
Arthritis Rheumatol. 2018 Jul;70(7):1000-1007. doi: 10.1002/art.40451. Epub 2018 May 11.
Many patients with rheumatoid arthritis (RA) report pain despite excellent control of inflammation with immunotherapies. Variable degrees of coexisting fibromyalgia (FM) may explain this disparity. FM has been characterized by aberrant brain functional connectivity, especially between the default mode network (DMN) and insula. We undertook this study to test the hypothesis that RA patients with the highest 2011 American College of Rheumatology FM survey criteria scores-a continuous measure of the degree of FM also known as "fibromyalgianess" (FMness)-would demonstrate functional connectivity abnormalities similar to those in FM.
RA patients underwent an 11-minute functional connectivity magnetic resonance imaging (MRI) brain scan and a clinical evaluation which included a measure of FMness. Brain networks were isolated from functional connectivity MRI data. Individual patient network-to-whole brain connectivity analyses were then conducted, followed by group-level regression, which correlated the connectivity of each network with FMness. Results were significant on the cluster level with a family-wise error (FWE) rate P value less than 0.05 derived from an uncorrected voxel-level P value less than 0.001.
A total of 54 patients participated (mean age 54.9 years, 75.9% women, mean FMness score 13.2 [range 1-29]). From the whole brain analyses, a single significant positive correlation between DMN connectivity to the left mid/posterior insula and FMness (r = 0.58, FWE-corrected P = 0.001) was demonstrated.
RA patients who have increased levels of FMness appear to share neurobiologic features consistently observed in FM patients. This study is the first to provide neuroimaging evidence that RA is a mixed pain state, with many patients' symptoms being related to the central nervous system rather than to classic inflammatory mechanisms.
许多类风湿关节炎 (RA) 患者尽管免疫治疗能很好地控制炎症,但仍有疼痛报告。共存的不同程度纤维肌痛 (FM) 可能解释了这种差异。FM 的特征是异常的大脑功能连接,特别是默认模式网络 (DMN) 和脑岛之间。我们进行这项研究是为了验证以下假设:2011 年美国风湿病学会 (ACR) 纤维肌痛调查标准评分最高的 RA 患者(FM 程度的连续衡量标准,也称为“纤维肌痛程度”)表现出与 FM 相似的功能连接异常。
RA 患者接受了 11 分钟的功能连接磁共振成像 (MRI) 脑扫描和临床评估,其中包括 FM 程度的测量。从功能连接 MRI 数据中分离出大脑网络。然后进行个体患者网络与全脑连接分析,接着进行组级回归,将每个网络的连接与 FM 程度相关联。结果在簇水平上具有统计学意义,采用未校正体素水平 P 值小于 0.001 衍生的校正后错误率 (FWE) P 值小于 0.05。
共有 54 名患者参与(平均年龄 54.9 岁,75.9%为女性,平均 FM 程度评分为 13.2[范围 1-29])。从全脑分析中,DMN 与左侧中/后脑岛的连接与 FM 程度呈显著正相关(r = 0.58,FWE 校正后 P = 0.001)。
FM 程度增加的 RA 患者似乎具有与 FM 患者一致观察到的神经生物学特征。这项研究首次提供了神经影像学证据,表明 RA 是一种混合疼痛状态,许多患者的症状与中枢神经系统有关,而不是与经典炎症机制有关。