Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia
Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia
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DOI：
10.1002/art.41069
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发表时间：
2019-11-26
影响因子：
13.3
通讯作者：
Basu, Neil
中科院分区：
文献类型：
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作者：
Kaplan, Chelsea M.;Schrepf, Andrew;Basu, Neil
目的风湿性关节炎（RA）伴发纤维肌痛（FM）患者存在中枢敏感化的脑连接改变。本研究的目的是探讨外周炎症，RA的主要伤害性刺激，如何与FM RA患者的大脑连接相互作用。方法对伴有FM和不伴有FM（FM+和FM-;每组n = 27）的RA患者进行功能连接性磁共振成像。使用来自左侧中/后额叶和左侧顶下小叶（IPL）的种子进行种子到全脑功能连接分析，这些区域先前分别与FM症状和炎症相关。在每组中分别评估功能连接性和红细胞沉降率（ESR）之间的相关性，然后进行事后分析以检验相互作用效应。如果P值小于0.05，则认为患者水平的家族错误（FWE）率具有显著性。结果RA伴FM组与不伴FM组在年龄、性别、血沉等方面差异无统计学意义（P > 0.2）。在FM+ RA患者中，岛叶-左侧IPL、左侧IPL-背侧前扣带回和左侧IPL-内侧前额叶皮质区域的功能连接增加与ESR水平升高相关（所有FWE校正P < 0.05）。事后交互分析在很大程度上证实了ESR和连接变化之间的关系，FM分数增加。结论我们首次报道了类风湿性关节炎中的FM可能通过脑连接的原伤害性模式与外周炎症有关的神经生物学证据。在这种“自下而上”疼痛集中的患者中，伴随症状可能对药物治疗有部分反应。
Objective Rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) exhibit alterations in brain connectivity synonymous with central sensitization. This study was undertaken to investigate how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with FM. Methods RA patients with concomitant FM and those without FM (FM+ and FM-, respectively; n = 27 per group) underwent functional connectivity magnetic resonance imaging. Seed-to-whole-brain functional connectivity analyses were conducted using seeds from the left mid/posterior insula and left inferior parietal lobule (IPL), which are regions that have been previously linked to FM symptoms and inflammation, respectively. The association between functional connectivity and erythrocyte sedimentation rate (ESR) was assessed in each group separately, followed by post hoc analyses to test for interaction effects. Cluster-level, family-wise error (FWE) rates were considered significant if the P value was less than 0.05. Results The group of RA patients with FM and those without FM did not differ by age, sex, or ESR (P > 0.2). In FM+ RA patients, increased functional connectivity of the insula-left IPL, left IPL-dorsal anterior cingulate, and left IPL-medial prefrontal cortex regions correlated with higher levels of ESR (all FWE-corrected P < 0.05). Post hoc interaction analyses largely confirmed the relationship between ESR and connectivity changes as FM scores increased. Conclusion We report the first neurobiologic evidence that FM in RA may be linked to peripheral inflammation via pronociceptive patterns of brain connectivity. In patients with such "bottom-up" pain centralization, concomitant symptoms may partially respond to antiinflammatory treatments.