Differential Activation in Amygdala and Plasma Noradrenaline during Colorectal Distention by Administration of Corticotropin-Releasing Hormone between Healthy Individuals and Patients with Irritable Bowel Syndrome.
Differential Activation in Amygdala and Plasma Noradrenaline during Colorectal Distention by Administration of Corticotropin-Releasing Hormone between Healthy Individuals and Patients with Irritable Bowel Syndrome.
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DOI：
10.1371/journal.pone.0157347
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Fukudo S
中科院分区：
文献类型：
--
作者：
Tanaka Y;Kanazawa M;Kano M;Morishita J;Hamaguchi T;Van Oudenhove L;Ly HG;Dupont P;Tack J;Yamaguchi T;Yanai K;Tashiro M;Fukudo S
肠易激综合征（IBS）通常伴随情绪和焦虑障碍。促肾上腺皮质激素释放激素（CRH）是脑-肠轴应激反应的主要介质，但CRH激动剂如何改变人脑对内感受性刺激的反应尚不清楚。我们验证了一种假设，即与健康对照组相比，在IBS患者中注射CRH后，大脑对结直肠膨胀的反应增强。16名男性IBS患者和16名年龄匹配的男性对照者在基线时进行脑H215O-正电子发射断层扫描（PET），使用气压袋充气，无膨胀，轻度和强烈的结肠膨胀。然后静脉注射CRH （2 μg/kg）或生理盐水（1:1），重复相同的扩张方案。每次刺激时测定血浆促肾上腺皮质激素（ACTH）、血清皮质醇和血浆去甲肾上腺素水平。在基线时，没有结肠膨胀的CRH诱导IBS患者右侧杏仁核的激活比对照组更多。在注射CRH后的剧烈腹胀期间，对照组在右侧杏仁核的激活程度明显高于IBS患者。血浆ACTH和血清皮质醇分泌显示药物（CRH、生理盐水）与腹胀之间有显著的相互作用。在IBS中，与注射前相比，注射CRH后血浆去甲肾上腺素基线水平显著升高。此外，血浆去甲肾上腺素表现出明显的药胀相互作用组（IBS，对照组）。在IBS患者和健康个体中，外源性CRH对内脏疼痛基质中情绪唤醒回路的脑区对结肠膨胀和去肾上腺素能功能的协同激活具有不同的敏感性。
Irritable bowel syndrome (IBS) often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET) was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg) or saline (1:1) was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH), serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline) and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls) by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.