Dietary monosodium glutamate increases visceral hypersensitivity in a mouse model of visceral pain

Abstract

BackgroundMonosodium glutamate (MSG) has been identified as a trigger of abdominal pain in irritable bowel syndrome (IBS), but the mechanism is unknown. This study examined whether MSG causes visceral hypersensitivity using a water‐avoidance stress (WAS) mouse model of visceral pain.MethodsMice were divided into four groups receiving treatment for 6 days: WAS + MSG gavage, WAS + saline gavage, sham‐WAS + MSG gavage, and sham‐WAS + saline gavage. The acute effects of intraluminal administration of 10 μM MSG on jejunal extrinsic afferent nerve sensitivity to distension (0–60 mmHg) were examined using ex vivo extracellular recordings. MSG was also applied directly to jejunal afferents from untreated mice. Glutamate concentration was measured in serum, and in the serosal compartment of Ussing chambers following apical administration.Key ResultsAcute intraluminal MSG application increased distension responses of jejunal afferent nerves from mice exposed to WAS + MSG. This effect was mediated by wide dynamic range and high‐threshold units at both physiologic and noxious pressures (10–60 mmHg, p < 0.05). No effect of MSG was observed in the other groups, or when applied directly to the jejunal afferent nerves. Serum glutamate was increased in mice exposed to WAS + MSG compared to sham‐WAS + saline, and serosal glutamate increased using WAS tissue (p = 0.0433).Conclusions and InferencesThese findings demonstrate that repeated exposure to MSG in mice leads to sensitization of jejunal afferent nerves to acute ex vivo exposure to MSG. This may contribute to visceral hypersensitivity reported in response to MSG in patients with IBS.

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“…Glutamate (the main component in MSG) and associated "dietary excitotoxin" chemicals such as aspartate have been linked to pain sensitivity and various neuropsychiatric symptoms, possibly because these agents can overexcite neurons [244]; a large number of pre-clinical studies support the idea that MSG can influence pain and lead to abnormal behavior in animals, including those that mimic depression and/or anxiety [245][246][247]. Recent human studies have found that the elimination/low intake of excitotoxin additives, including aspartame and MSG or MSG-like chemicals, can improve symptoms of depression, anxiety, posttraumatic stress disorder (PTSD) [248,249], and fibromyalgia [250]; this includes improved depression, anxiety, and cognitive function and reduced pain sensitivity in veterans with Gulf War Illness [251][252][253].…”

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“…There are numerous mechanisms by which glutamate, the primary component of MSG, might cause neuropsychiatric symptoms, although the most obvious is that the chemical, and related dietary excitotoxins such as aspartame, cause overexcitation of neurons (Olney 1990;Rycerz and Jaworska-Adamu 2013); a growing number of animal studies indicate that oral MSG and aspartame can lead to abnormal behaviors in animals, including those that mimic depression and/or anxiety (Chakraborty 2019;Kraal et al 2020;Brant et al 2023;Ashok et al 2014;Choudhary and Lee 2018;Erbaş et al 2018;Jones et al 2022;Fowler et al 2023; O.J. Onaolapo et al 2012).…”

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“…These chemicals, referred to as excitotoxins because of their capacity to overexcite neurons, have been associated with pain sensitivity and neuropsychiatric symptoms; and it has been hypothesized that differences in blood-brain barrier permeability in various non-communicable diseases might determine the presence/absence of dietary excitotoxin symptomology [173,174]. Multiple pre-clinical studies show that MSG has the potential to have deleterious effects on nervous symptom function, including heightened pain sensitivity, and alterations to animal behaviors that reflect human depression and/or anxiety [175][176][177]. The consumption of foods and beverages containing dietary additives continues to grow in the US; perhaps most concerning is a reported 20% increase in the proportion of baby food purchases containing additives and an over 15% increase in the proportion of purchases containing three or more dietary additives [160].…”

“…These chemicals, referred to as excitotoxins because of their capacity to overexcite neurons, have been associated with pain sensitivity and neuropsychiatric symptoms; and it has been hypothesized that differences in blood-brain barrier permeability in various non-communicable diseases might determine the presence/absence of dietary excitotoxin symptomology [173,174]. Multiple pre-clinical studies show that MSG has the potential to have deleterious effects on nervous symptom function, including heightened pain sensitivity, and alterations to animal behaviors that reflect human depression and/or anxiety [175][176][177].…”