Mast cells and neuropeptidergic terminals: Experimental studies of the mechanism of visceral hypersensitivity in irritable bowel syndrome

Abstract

OBJECTIVE: The failure of dysmotility to explain the symptoms of pain in irritable bowel syndrome (IBS) led to studies on visceral hypersensitivity. Mucosal mast cells (MC) may be one factor influencing the response of visceral afferents to mechanical and chemical stimuli because they are found in close proximity to gastrointestinal mucosal sensory nerve terminals containing neuropeptides and a bi‐directional pathway linking the central nervous system, gut and MC has been demonstrated. METHODS: The present study investigated the extent of MC and the neuropeptides, substance P (SP) and vasoactive intestinal peptide (VIP), in the intestinal mucosa of patients with IBS, as well as the location of the MC. The MC and neuropeptidergic terminals were stained histochemically and immunohistochemically, respectively, neuropeptide concentrations were measured by radioimmunoassay (RIA), and the results were investigated qualitatively and quantitatively by color image analyzer. The structural relation between the MC and neuropeptide terminals was studied by ultramicroscopy using in situ embedding technique. RESULTS: In IBS, the number of MC in the terminal ileum, the ileocecal junction, and the ascending colon was significantly increased (P < 0.01), and the MC had great variations in their extent and size. Significantly increased concentrations of VIP and SP were found in the colon of IBS patients compared with controls. A correlation between mucosal MC and the SP(VIP)‐ergic terminals was found, and the MC were close to these terminals in the lamina propria, which demonstrated SP (VIP)‐ergic terminals. CONCLUSIONS: Mast cells and the neuropeptides of intestinal mucosa may play a central role in gut hypersensitivity, resulting in both the motor response and visceral perceptions that occur with IBS.