Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland.
Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
PLoS One. 2013 Dec 18;8(12):e84718. doi: 10.1371/journal.pone.0084718. eCollection 2013.
The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders.
精神病学与应激相关胃肠道疾病（如肠易激综合征（IBS））之间的关系已经得到充分证实，焦虑症和抑郁症是最常见的合并症。此外，表现出焦虑和抑郁样行为的应激敏感 Wistar Kyoto（WKY）大鼠表现出类似于应激相关胃肠道疾病中观察到的胃肠道紊乱。此外，越来越多的临床前和临床证据表明肥大细胞是 IBS 中腹部内脏疼痛发展的重要贡献者。在这项研究中，我们研究了大鼠结缔组织肥大细胞（CTMC）稳定剂二钠色甘酸钠（DSCG）对内脏敏感性和结肠离子转运的影响，并检查了应激敏感 WKY 大鼠的结肠和腹膜肥大细胞。DSCG 可显著降低 WKY 动物结直肠扩张引起的腹痛行为，而不减少结肠大鼠肥大细胞介质的释放。我们进一步证明，肥大细胞刺激的结肠离子转运对肥大细胞稳定剂 DSCG 敏感，仅在应激敏感大鼠中观察到这种作用。此外，WKY 动物的结肠黏膜下层中 CTMC 样肥大细胞明显增加，与对照动物相比，中间或不成熟的腹膜肥大细胞的比例显著增加。总的来说，我们的数据进一步支持肥大细胞在应激相关胃肠道疾病发病机制中的作用。
