Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2010 Jan 5;5(1):e8573. doi: 10.1371/journal.pone.0008573.
Although visceral pain of gastrointestinal (GI) origin is the major complaint in patients with irritable bowel syndrome (IBS) it remains poorly understood. Brain imaging studies suggest a defect in brain-gut communication in IBS with a greater activation of central arousal circuits including the amygdala. Previously, we found that stereotaxic implantation of corticosterone (CORT) onto the amygdala in rats induced anxiety and colonic hypersensitivity. In the present study we used functional magnetic resonance imaging (fMRI) to identify specific brain sites activated in a rat model characterized by anxiety and colonic hypersensitivity.
METHODOLOGY/PRINCIPAL FINDINGS: Anesthetized male rats received micropellets (30 microg each) of either CORT or cholesterol (CHOL), to serve as a control, implanted stereotaxically on the dorsal margin of each amygdala. Seven days later, rats were anesthetized and placed in the fMRI magnet (7T). A series of isobaric colorectal balloon distensions (CRD - 90s 'off', 30s 'on', 8 replicates) at two pressures (40 and 60 mmHg) were performed in a standard block-design. Cross correlation statistical analysis was used to determine significant differences between distended and non-distended states in CORT and CHOL-treated animals. Analysis of the imaging data demonstrated greater overall brain activation in response to CRD in rats with CORT implants compared to CHOL controls. Additionally, CORT implants produced significant positive bilateral increases in MRI signal in response to CRD in specific nuclei known as integration sites important in anxiety and pain perception.
These data indicate that chronic exposure of the amygdala to elevated levels of CORT enhances overall brain activation in response to CRD, and identified other specific brain regions activated in response to mechanical distension of the colon. These results demonstrate the feasibility of performing fMRI imaging in a rodent model that supports clinical observations in IBS patients with enhanced amygdala activation and symptomatology of abdominal pain and anxiety.
尽管胃肠道（GI）来源的内脏疼痛是肠易激综合征（IBS）患者的主要主诉，但仍知之甚少。脑成像研究表明，IBS 存在脑-肠通讯缺陷，中枢觉醒回路（包括杏仁核）的激活增加。先前，我们发现立体定向植入大鼠杏仁核的皮质酮（CORT）会引起焦虑和结肠高敏性。在本研究中，我们使用功能磁共振成像（fMRI）来鉴定在以焦虑和结肠高敏性为特征的大鼠模型中激活的特定脑区。
方法/主要发现：麻醉雄性大鼠接受立体定向植入每个杏仁核背侧边缘的皮质酮（CORT）或胆固醇（CHOL）微球（每个 30μg），作为对照。7 天后，大鼠被麻醉并放置在 fMRI 磁体（7T）中。在标准的块设计中，对两种压力（40 和 60mmHg）下的等压结直肠球囊扩张（CRD-90s“关闭”，30s“打开”，8 个重复）进行了一系列操作。使用交叉相关统计分析来确定 CORT 和 CHOL 处理动物在扩张和非扩张状态之间的显著差异。对成像数据的分析表明，与 CHOL 对照相比，CORT 植入大鼠对 CRD 的反应具有更大的整体大脑激活。此外，CORT 植入物在对 CRD 的反应中，在对焦虑和疼痛感知很重要的特定核中产生了双侧显著的正 MRI 信号增加。
这些数据表明，杏仁核长期暴露于高水平的 CORT 会增强对 CRD 的整体大脑激活，并确定了对结肠机械扩张的其他特定脑区的激活。这些结果表明，在支持 IBS 患者杏仁核激活增强和腹痛及焦虑症状的临床观察的大鼠模型中进行 fMRI 成像具有可行性。
