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Study Sheds Light on the Causes of Debilitating Gut Pain

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Debilitating gut pain is common, but the underlying cause is still unclear. Usually, it stems from a gut infection that triggers immune responses. These may cause everyday food to be deemed as harmful, causing severe and persistent pain.

A new study, published in the journal Nature, reports evidence from mice and humans that a novel mechanism contributes to chronic gut pain.

Chronic Gut Pain

Pain occurs to alert the body and protect it from actual or potential tissue damage. There are three common forms of pain – nociceptive pain, caused by damage to body tissue. Inflammatory pain, normal inflammation caused by an inappropriate response by the body's immune system, and chronic pain, defined as pain that lasts at least 12 weeks.

One of the most common causes of chronic gut pain is irritable bowel syndrome (IBS), which causes cramping, diarrhea, and constipation. The chronic pain in this condition is often attributed to allergies, but there is no exact cause and mechanism for why it happens.

Often, the pain related to IBS can't be easily pinpointed, and it is hard to determine the cause or origin of the pain. Usually, people who have pain in their internal organs face the problem of not knowing its root cause. For instance, IBS, a condition that affects about 11 percent of the world population, does not have specific illness hallmarks, which will distinguish one disease from another.

IBS can be triggered by risk factors like imbalance in the gut flora and gastroenteritis due to the ingestion of contaminated food or water, stress, and gut-brain communication changes.

The study researchers also found that a bacterial infection can alter immune responses in the gut, resulting in some foods being perceived as harmful. As a result, the body attacks the food and surrounding tissues, causing persistent gut pain.

The Study

In the study, the researchers at the Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing in Belgium, explain the new mechanism, wherein a gut infection alters how the organ tolerates antigens, which can be found in many food items.

The immune system of the intestines will detect these antigens as harmful. As a result, people with IBS feel pain whenever they consume foods. They also showed that bacterial infection and bacterial toxins could induce an immune response that triggers the production of dietary-antigen-specific immunoglobulin E (IgE) antibodies in mice.

After ingesting the dietary antigen, visceral pain appeared. The pain signaling came from the histamine receptor H1-mediated sensitization of visceral afferents. Further, food antigen injection, including wheat, soy, milk, and gluten, into the mucosa of patients with IBS triggered local edema and mast cell activation, which are hallmarks of inflammation.

After infection, the team also found that the egg white protein stimulated a chain reaction akin to what happens during a food allergy. The antigen attached itself to the antibodies IgE, which are connected to mast cells.

"Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders," the researchers concluded in the study.

Along with their findings, the researchers suggested several options for treatment. First, they recommended improving the intestinal-barrier function to reduce the gut's access to the intestinal immune system. Second, they suggested targeting IgE antibodies that could trigger inflammation and are specific to the food of interest, targeting the molecules released by the mast cells. Lastly, they recommended blocking the colonic sensory nerves that transmit information to the brain to cause pain.

The team said that further research is needed to help develop therapeutics to help people with IBS.

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Schedule30 Sep 2023