Nerve growth factor content is increased in the rectal mucosa of children with diarrhea-predominant irritable bowel syndrome

Background The enteric nervous system is a complex network that includes, in the digestive mucosa, neuronal bodies and fibers interacting with the immune system and mucosal mast cells (MC). These interactions involve the secretion of messengers, such as the neurotrophin nerve growth factor (NGF), which influence colonic motility and sensitivity, both affected in irritable bowel syndrome (IBS). This study was designed to test the hypothesis that, in children with IBS, colonic mucosal innervation, NGF content, and MC infiltration are altered. We aimed to measure MC infiltration, number of neuronal bodies, distance from MC to nerve fibers, inflammation, and NGF content in rectal mucosa of pediatric patients with IBS as compared with controls. Methods Rectal biopsies from children (median age: 14 years) with diarrhea-predominant IBS (n = 11) and controls (n = 14) were studied. MC and neuronal mucosal structures were identified by tryptase, CD117 and PGP9.5 immunoreactivity. Inflammatory cells (neutrophils, eosinophils, and lymphocytes) were counted. NGF was quantified in situ by ELISA. Key Results No mucosal inflammation was detected in IBS. MC infiltration and number of neuronal bodies were not significantly different between IBS and controls. The distance between MC and nerve fibers was not different in IBS compared with controls (5.2 +/- 0.3 vs 5.0 +/- 0.3 mu m). Number of MC in close proximity to nerve fibers (<5 mu m) was not different in the two groups. However, in IBS, NGF content was higher than controls (0.93 +/- 0.3 vs 0.62 +/- 0.3 pg mg-1 protein, P < 0.05) and significantly correlated with MC number. Conclusions & Inferences Regardless of inflammation, NGF content is increased in rectal mucosa of diarrhea-predominant IBS children.