Nerve fiber overgrowth in patients with symptomatic diverticular disease

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.