title: Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain.
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.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland.
authors.forename: Siobhan Yvonne
authors.initials: SY
authors.lastname: Carroll
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
authors.forename: Siobhain Mary
authors.initials: SM
authors.lastname: O'Mahony
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Grenham
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
authors.forename: John Francis
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland.
authors.forename: Niall Patrick
authors.initials: NP
authors.lastname: Hyland
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy* / Q000209:etiology; D000704:Analysis of Variance; D000818:Animals; D003106:Colon / Q000503:physiopathology*; D004205:Cromolyn Sodium / Q000494:pharmacology* / Q000627:therapeutic use; D006967:Hypersensitivity / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D007150:Immunohistochemistry; D017136:Ion Transport / Q000187:drug effects*; D008407:Mast Cells / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
chemical_list: D004205:Cromolyn Sodium