The abdominal pain that accompanies irritable bowel syndrome (IBS) is thought to have both central and peripheral nerve origins, with the peripheral mechanism involving hypersensitivity of the intestinal wall. The causes of this hypersensitivity are unknown, but mediators from intestinal mast cells may play a significant role. This human study examined mechanisms by which mast cells may activate visceral sensory nerves in IBS patients. Mucosal biopsies of 29 patients with IBS and 15 controls were performed. Immunofluorescence and immunoenzymatic assays were used to evaluate colonic mast cell infiltration and mediator release. The effect of the mucosal mediators-histamine, tryptase, and prostaglandin E2 (PGE2)-on mesenteric sensory nerve firing and Ca2+ mobilization in rat dorsal root ganglia was assessed. The authors observed an influx of mast cells in the colonic mucosa of IBS patients, with a close proximity of the mast cells to nerve fibers. Release of mast cell mediators was also increased, as a result of either the higher number of mast cells in the mucosa or increased activation of mast cells, although what causes the increased mast cell infiltration/activation is unknown. In addition, mediators released from IBS colonic mucosa were found to induce increased excitation of mesenteric afferent nerves and of nociceptive neurons of rat dorsal root ganglia (shown by enhanced Ca2+ mobilization) when compared to controls. Histamine-1 receptor blockade and serine protease inactivation significantly reduced these effects, although not completely, thus suggesting that additional mediators may be involved. These data may provide new understanding of the pathophysiology of IBS.
COMMENTARY: Fortunately, we do not have to deal with IBS much in veterinary medicine; when we do, it is a diagnosis of exclusion and one always worries that something more tangible may have been overlooked. The cause of the disease has been problematic because of an association with "stress" or with hormonal issues. Increasing evidence suggests that IBS may well be an inflammatory disease. I have previously commented on articles showing that numbers of eosinophils and mast cells are increased around the enteric nerves in IBS patients, that increased inflammatory cytokines are found in the blood of patients compared with controls, and that these cytokines are reduced by probiotics. Now comes this startling and revolutionary piece of evidence for the involvement of mast cells and their metabolites. Imagine the sensitivity of a system in which mast cell mediators from colonic biopsy specimens from IBS patients excite rat nociceptive visceral sensory nerves. It is too soon to speculate on the implications for veterinary medicine, but it does give us powerful insights into the mechanisms of visceral pain.
Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Barbara G, Wang B, Stanghellini V, et al. GASTROENTEROLOGY 132:26-37, 2007.