Abstract
BackgroundAbdominal pain of unknown origin affects up to 20% of school-aged children. Evaluation of children is symptom-based without clear guidelines to investigate molecular mechanisms of abdominal pain. Aberrant molecular mechanisms may increase intestinal permeability leading to interactions between the immune and nervous systems, subclinical inflammation, and visceral pain. This study evaluated the association between interleukin-6 (IL-6), mast cell infiltrates, and serotonin (5-HT) levels in gastrointestinal (GI) biopsies, with perceived abdominal pain in a pediatric cohort.MethodsClinical data and biopsy samples from pediatric patients (n = 48) with chronic abdominal pain, with and without inflammation were included. Formalin-fixed paraffin-embedded GI biopsies were sectioned and immunohistochemistry performed for IL-6 and 5-HT; mast cells were identified with toluidine blue stain. Histological findings were compared to self-reported abdominal pain between groups.ResultsThere was significantly greater IL-6 immunoreactivity in biopsies with confirmed histologic inflammation (p = 0.004). There was a greater number of mast cells per HPF in non-inflammatory biopsies (3.5 ± 2.9) compared to the inflammatory biopsies (2.6 ± 1.8) p = 0.049. The non-inflammatory biopsy group was significantly less likely to respond to standard treatment as evidenced by higher pain reports (p = .018). Mast cells (p = .022) and 5-HT (p = .02) were significantly related to abdominal pain scores.ConclusionsA potential association between self-reported abdominal pain, number of mast cells, and 5-HT levels, which may contribute to perceived GI pain in pediatric patients may exist.
Highlights
Abdominal pain of unknown origin affects up to 20% of school-aged children
The mechanisms of chronic abdominal pain of unknown origin may be related to interactions between the immune and nervous system in the gut thereby leading to visceral hypersensitivity of the intestinal mucosa [8]
22 pediatric GI biopsies were categorized as inflammatory and 26 pediatric GI biopsies as non-inflammatory which coincided with the original clinical diagnosis of disease
Summary
Abdominal pain of unknown origin affects up to 20% of school-aged children. Evaluation of children is symptom-based without clear guidelines to investigate molecular mechanisms of abdominal pain. Aberrant molecular mechanisms may increase intestinal permeability leading to interactions between the immune and nervous systems, subclinical inflammation, and visceral pain. The mechanisms of chronic abdominal pain of unknown origin may be related to interactions between the immune and nervous system in the gut thereby leading to visceral hypersensitivity of the intestinal mucosa [8]. A study conducted by Mahjoub, et al found increased mast cell density in pediatric patients with recurrent abdominal pain [14]. They propose that mast cell density measurements be incorporated with routine GI biopsies due to a significant correlation between increase GI complaints and mast cell count. Inflammation and increased permeability of GI tract mucosa may induce pain in pediatric patients with functional abdominal pain [15]
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