A102 MONOSODIUM GLUTAMATE INCREASES VISCERAL SENSITIVITY IN A MURINE MODEL OF IRRITABLE BOWEL SYNDROME

Abstract Background Over 70% of patients suffering from symptoms of the irritable bowel syndrome (IBS) report that food is the most common trigger. Patients have identified that monosodium glutamate (MSG) is one food component that they suspect can trigger symptoms, but this remains unproven. As a first step towards establishing a potential role, we sought to examine whether there was a plausible mechanism of how MSG ingestion could underlie exaggerated pain signaling in IBS. Aims To examine the effects of MSG on visceral sensitivity in a murine model of IBS. Methods Balb/c mice were subjected to 6-days of water-avoidance stress (WAS) to create a pre-clinical model for IBS. To assess changes in visceral afferent nerve sensitivity in control and WAS mice, responses to ramp distension (0–60 mmHg), in the absence and presence 10 μM MSG perfused into the intestinal lumen (concentration based on diet analysis of MSG human ingestion), were recorded from afferent nerves innervating the jejunum ex vivo. To quantify these responses, the baseline firing frequency (spikes/second) was subtracted from the maximum response at each distending pressure. The relative distension response was calculated as a percentage of the control distension response (absence of MSG) (Figure 1). Jejunal preparations from the same WAS-treated mice were also used to measure ex vivo changes in mucosal permeability to MSG using Ussing chambers. We also ran the same distension protocol; however, we applied 10 μM MSG directly to the organ bath outside intestine obtained from control mice. This direct application would allow the MSG to have direct access to the nerve terminals without having to traverse the mucosa. Results The intraluminal administration of 10 μM MSG significantly increased afferent nerve sensitivity in WAS-treated jejunum but not controls. This response was significantly greater (23%) at pressures between 40 and 60 mmHg (p<0.01) (Figure 1). WAS-treated mouse jejunum was also significantly more permeable to MSG (p<0.05). Furthermore, the application of 10 μM MSG directly to the bath containing healthy jejunum significantly increased by 25% the sensitivity of afferent nerves specifically at 60 mmHg (p<0.01). Conclusions Our findings demonstrate that MSG increases visceral sensitivity to distension in our pre-clinical model of IBS. The increased permeability to MSG in WAS tissue and increased distension response in healthy control tissue when MSG is applied directly to the bath rather than intraluminally, suggests that MSG signals to the immune compartment or directly to the afferent nerve terminals. These findings support the rationale for future in vivo studies with this model to further clarify the mechanism. Funding Agencies CCC, CIHR

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