Nerve fiber overgrowth in patients with symptomatic diverticular disease

Abstract

Background Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula. Methods Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth‐associated protein 43, GAP43+fibers). Key Results No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+ fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells. Conclusions and Inferences Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.

Pathophysiology of Diverticular Disease: From Diverticula Formation to Symptom Generation

“…We evaluated nerve fiber density in the colonic mucosa of asymptomatic and symptomatic patients with DD, compared to healthy subjects, in a region close to a diverticulum (diverticular region) and in a site far from the diverticula. Nerve fibers, assessed as NSE positive fibers, were increased in patients with diverticula, irrespective of the presence of symptoms, compared to healthy subjects only in the diverticular region [ 93 ], which is in line with previous data [ 94 ].…”

Colonic diverticular disease

“…Colonic motility studies using 24 35 . Furthermore, in patients with SUDD but not in individuals with diverticulosis, nerve fibre sprouting was found to be increased in the region of diverticulosis, which might be the cause of visceral hypersensitivity and, therefore, be involved in symptom generation 62 . Addiyionally, the type I to type III collagen ratio, cross-linking of collagen fibrer 63 and levels of tissuedegrading matrix metalloproteinases 64 Third, two large population-based familial aggregation studies in Scandinavia found that the risk of hospitalization for diverticular disease was higher in the siblings of individuals with diverticular disease than in general population and higher in monozygotic twins than in dizygotic twins; these studies estimated that ~50% of the risk for diverticular disease [Au: is this a risk for incidence or for hospitalization?…”

S3-Leitlinie Divertikelkrankheit/Divertikulitis – Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV)

“…Gliazellen im Kolon ohne Nachweis von neuronalen Auffälligkeiten und eine Erniedrigung der elektrischen slow wave Aktivität mit resultierendem verlangsamtem Transit beschrieben. Auch eine Vermehrung von Nervenfasern im enterischen Nervensystem konnte nachgewiesen werden 170 171 .…”