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Biomarkers in Children with Chronic Abdominal Pain

There are molecular differences beneath the surface of childhood abdominal pain and identifying them may lead to better diagnosis and novel treatments, according to a study by NINR intramural researchers.

Between 10-30 percent of children from age 4-16 years report chronic abdominal pain that is not associated with an inflammatory gastrointestinal (GI) condition. Many of these pediatric patients undergo multiple therapies to alleviate their pain. Yet despite treatment, some children often continue to experience pain.

A team led by Dr. Wendy Henderson, chief of NINR’s Division of Intramural Research’s Digestive Disorders Unit, set out to identify the biomarkers of undiagnosed chronic abdominal pain in children. The team collected tissue samples from pediatric patients who were experiencing chronic abdominal pain and divided these samples into two groups based on the presence or absence of microscopic evidence of inflammation. Then they examined the samples for interleukin-6 (IL-6), mast cells, enterochromaffin cells, serotonin, and Substance P and looked for differences between the two groups.

“We chose to examine these biomarkers because other studies have indicated they may be associated with inflammation at the molecular level. Because the molecular inflammatory process may not be detectable in every GI patient who experiences chronic pain,” said Henderson, “we suspected the molecular expression of these biomarkers might vary in children with chronic abdominal pain, regardless of the presence or absence of inflammation.”

The study, published in the World Journal of Gastrointestinal Pathophysiology, found elevated levels of IL-6 in patients with inflammation, as was expected based on past studies. Yet they also found an increased mast cell count in patients without inflammation. This inverse relationship between the two markers, IL-6 and mast cells, in patients with microscopic inflammation versus those without, was seen only in biopsies from the lower GI regions.

The researchers found no differences between the two groups regarding levels of enterochromaffin cells, serotonin, and substance P. However, substance P, which increases colonic propulsive movement and stimulates smooth muscles, was found in the superficial GI mucosa layers of the patients without inflammation. Substance P was also expressed more often in the biopsies of female patients versus male.

 “These novel findings suggest there are molecular differences in the subclinical pathology of abdominal pain disorders,” said Dr. Henderson. “Although more research is needed, evaluating these and other biomarkers may eventually help us develop effective, individual treatment programs based on the biological characteristics of each pediatric patient.”

To read the abstract, visit

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