Pain matrix shift in the rat brain following persistent colonic inflammation revealed by voxel-based statistical analysis
Pain matrix shift in the rat brain following persistent colonic inflammation revealed by voxel-based statistical analysis
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DOI：
10.1177/1744806919891327
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发表时间：
2019-11-01
期刊：
影响因子：
3.3
通讯作者：
Cui, Yilong
中科院分区：
文献类型：
--
作者：
Huang, Tianliang;Okauchi, Takashi;Cui, Yilong
炎症性肠病（Inflammatory bowel disease，IBD）是以消化道慢性炎症为特征的疾病，主要包括克罗恩病（Crohn's disease）和溃疡性结肠炎（ulcerative colitis）。大约60%的患者在急性IBD发作期间经历腹痛，这严重损害了他们的生活质量。外周和中枢机制都被认为参与了IBD的腹痛。虽然在IBD的病理生理学中，腹痛的外周机制已引起广泛关注，但对脊髓上机制的参与仍知之甚少。为了解决这个问题，我们研究了正常和IBD模型大鼠结直肠扩张时的局部脑活动，使用基于体素的2-脱氧-2-[18 F]氟-（D）-葡萄糖正电子发射断层扫描成像的统计分析。大鼠IBD模型通过结肠直肠给药2，4，6-三硝基苯磺酸（一种广泛用于产生结肠炎的化合物）产生。注射2，4，6-三硝基苯磺酸后可引起组织损伤和炎症反应，并随时间发生动态变化，而结直肠扩张引起的内脏反应也有相应的时间变化。我们发现，内脏无害和有害的结直肠扩张和脊髓上的伤害性刺激都有特征性的脑激活，它们共享一些生理感觉通路。IBD大鼠伤害性结直肠扩张后，广泛的脑区被激活，丘脑中央内侧核与前扣带回之间的功能耦合增强。在正常和IBD大鼠中，前岛叶皮层和前扣带皮层的脑活动增加分别与伤害性结直肠扩张引起的疼痛严重程度呈正相关。这些结果表明，持续性结肠炎后痛基质发生了转移，丘脑中央内侧核至前扣带回通路中的丘脑皮层敏感化可能是IBD内脏痛觉过敏的一个重要病理生理机制。
Inflammatory bowel disease (IBD), mainly comprising Crohn's disease and ulcerative colitis, is characterized by chronic inflammation in the digestive tract. Approximately 60% of the patients experience abdominal pain during acute IBD episodes, which severely impairs their quality of life. Both peripheral and central mechanisms are thought to be involved in such abdominal pain in IBD. Although much attention has been paid to peripheral mechanisms of abdominal pain in IBD pathophysiology, the involvement of supraspinal mechanisms remains poorly understood. To address this issue, we investigated regional brain activity in response to colorectal distension in normal and IBD model rats using voxel-based statistical analysis of 2-deoxy-2-[18F]fluoro-(D)-glucose positron emission tomography imaging. The rat IBD model was generated by colorectal administration of 2,4,6-trinitrobenzene sulfonic acid, a chemical compound widely used to generate colitis. Tissue damage and inflammation were induced and dynamically changed with time after 2,4,6-trinitrobenzene sulfonic acid injection, while colorectal distension-induced visceromotor response showed corresponding temporal changes. We found that characteristic brain activations were observed in response to visceral innocuous and noxious colorectal distension and supraspinal nociception shared some physiological sensory pathway. Moreover, widespread brain regions were activated, and the functional coupling between the central medial thalamic nucleus and anterior cingulate cortex was enhanced after noxious colorectal distension in IBD model of rats. Increased brain activity in the anterior insular cortex and anterior cingulate cortex was positively correlated with noxious colorectal distension-induced pain severity in normal and IBD rats, respectively. These findings suggest that the pain matrix was shifted following persistent colonic inflammation, and thalamocortical sensitization in the pathway from the central medial thalamic nucleus to anterior cingulate cortex might be a central mechanism of the visceral hyperalgesia in IBD pathophysiology.