Abstract
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.
Highlights
Abdominal visceral pain and altered bowel habits are cardinal symptoms of the stress-related gastrointestinal (GI) disorder, irritable bowel syndrome (IBS) [1,2]
Colonic release mast cell mediators is insensitive to inhibition by disodium cromoglycate Vehicle-treated Wistar Kyoto (WKY) animals displayed significantly greater compound 48/80-stimulated rat mast cell protease II (RMCPII) release relative to vehicletreated Sprague Dawley rats (SD) tissues (t(13)=3.33, p
The compound 48/80-induced Isc response was significantly diminished in WKY colon relative to SD tissues (F (1,57),=77.69, p
Summary
Abdominal visceral pain and altered bowel habits are cardinal symptoms of the stress-related gastrointestinal (GI) disorder, irritable bowel syndrome (IBS) [1,2]. It is not surprising that rodent models of anxiety and depression, such as the Wistar Kyoto (WKY) rat [4], display GI features akin to those associated with IBS, for example increased abdominal visceral pain [5,6,7], reduced colonic accommodation [8] and altered colonic fluid and electrolyte transport [9,10], all key pathophysiological features which support the use of the WKY rat as a valid preclinical paradigm for examining stress-related GI disorders, and in particular IBS [11]. The evidence to date implicating mast cells in the pathogenesis and pathophysiology of IBS [12,13,14,15], and the contribution of their mediators to the development of visceral hypersensitivity [12,13,16,17] is robust, and supports the targeting of mast cells in the management of stress-related GI disorders. Given the association between stress-related GI disorders and altered bowel habit, we sought to examine the effects of DSCG on colonic secretory function in anxiety-prone WKY rats
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