MONOSODIUM GLUTAMATE INCREASES VISCERAL SENSITIVITY IN A PRECLINICAL MODEL OF IRRITABLE BOWEL SYNDROME
Patients with irritable bowel syndrome (IBS) have identified that monosodium glutamate (MSG) triggers symptoms of abdominal pain. I sought to use a preclinical model for IBS to study how MSG effects intestinal afferent nerve sensitivity. A preclinical model for IBS was developed in mice using a water-avoidance stress (WAS) protocol. To understand the effects of MSG on visceral sensitivity, ex vivo changes in extrinsic intestinal afferent nerve sensitivity to jejunal distension (0-60 mmHg) were measured. In the preliminary study, mice that were exposed to WAS had increased intestinal afferent nerve sensitivity in the presence of MSG (10 M) at noxious pressures (40-60 mmHg). This effect was mediated by increased activity in high-threshold (HT) units. With this preliminary evidence, I examined the effects of MSG on intestinal afferent nerve sensitivity in mice exposed to WAS and MSG gavage, WAS and saline gavage and sham-WAS and gavage controls. There was a significant increase in distension response in intestinal afferent nerves from mice exposed to WAS and MSG gavage at both physiologic and noxious pressures (10-60 mmHg). The increases in intestinal afferent nerve distension response were mediated by an increase in the activity in wide-dynamic range (WDR) and HT units. Serum glutamate levels were also increased in mice exposed to WAS and MSG gavage in comparison to other treatment groups; however, this did not reach significance. MSG had no significant effect in non-handled or sham-WAS controls. Applying MSG directly to the intestinal afferent nerves from healthy controls resulted in a significant increase in distension response. This effect again mediated by WDR and HT units. Ussing chamber permeability assays demonstrated that jejunal tissue from mice exposed to WAS was significantly more permeable to MSG in comparison to control. WAS exposure did not impact ex vivo FITC dextran permeability. Overall, these findings demonstrate that MSG increases visceral sensitivity in a pre-clinical model for IBS. The increase in visceral sensitivity is mediated by units that detect noxious stimuli and may be a result of increased permeability to MSG.