Liebregts Tobias, Adam Birgit, Bertel Anton, Lackner Carolin, Neumann Jens, Talley Nicholas J, Gerken Guido, Holtmann Gerald
Royal Adelaide Hospital, Department of Gastroenterology, Hepatology and General Medicine, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia.
Eur J Pain. 2007 Feb;11(2):216-22. doi: 10.1016/j.ejpain.2006.02.007. Epub 2006 Mar 20.
Lowered visceral sensory thresholds are a key finding in at least a subgroup of patients with functional bowel disorders. Stress and inflammation contribute to this altered visceral sensory function. We aimed to elucidate the role of repetitive stress and acute mucosal inflammation, alone and in combination, on sensory function.
In randomized order, trinitrobenzenesulfonic acid (TNBS) plus the equal amount of ethanol or saline were instilled into the colorectum of female Lewis rats. Colorectal distensions (CRD) were performed with a barostat device (3 min/40 mmHg); to quantify the visceromotor response (VMR) to CRD, electromyographic activity (EMG) of the abdominal muscles was recorded. In randomized order, equal numbers of both treatment groups underwent either seven days (1 h/day) repetitive water avoidance stress (WAS) or sham WAS. CRD's were conducted 28 days later. Colonic tissue samples were obtained to characterize inflammation and blood samples were taken at day 28 to measure plasma IL-2 levels by enzyme-linked immunosorbent assay (ELISA).
Compared to controls (662+/-114 microV) TNBS (1081+/-227 microV), WAS (1366+/-125 microV) and the combination of both (1477+/-390 microV) significantly augmented the VMR to CRD. TNBS and/or WAS caused significant inflammatory changes at day 5, while only TNBS+WAS also showed signs of mucosal inflammation on day 14 and significantly elevated IL-2 levels on day 28.
Stress and inflammation cause long lasting alterations of visceral sensory function. Concomitant stress further increases post-inflammatory visceral hyperalgesia.
内脏感觉阈值降低是至少一部分功能性肠病患者的关键发现。压力和炎症导致这种内脏感觉功能改变。我们旨在阐明重复性压力和急性黏膜炎症单独及联合作用对感觉功能的影响。
将三硝基苯磺酸（TNBS）加等量乙醇或生理盐水以随机顺序注入雌性Lewis大鼠结肠。使用压力控制装置进行结肠扩张（CRD，3分钟/40毫米汞柱）；为量化对CRD的内脏运动反应（VMR），记录腹肌的肌电图活动（EMG）。两个治疗组中数量相等的大鼠以随机顺序接受为期七天（每天1小时）的重复性避水应激（WAS）或假WAS。28天后进行CRD。获取结肠组织样本以表征炎症情况，并在第28天采集血样，通过酶联免疫吸附测定（ELISA）测量血浆白细胞介素-2水平。
与对照组（662±114微伏）相比，TNBS组（1081±227微伏）、WAS组（1366±125微伏）以及两者联合组（1477±390微伏）对CRD的VMR显著增强。TNBS和/或WAS在第5天引起显著炎症变化，而仅TNBS+WAS在第14天也显示出黏膜炎症迹象，并在第28天显著提高白细胞介素-2水平。
压力和炎症导致内脏感觉功能的长期改变。伴随的压力进一步增加炎症后的内脏痛觉过敏。
