Nerve remodeling and inflammation in diverticular disease

Abstract

Background and Aim: The enteric nervous system intrinsically coordinates digestion and integrates information from extrinsic autonomic innervation. Current research suggests that disrupted neural control of colonic motility plays a pathogenetic role in diverticular disease (DD). However, there are few studies that examine the fine structure of the enteric nervous system. Our aim was to study the ultrastructure of the enteric nervous system of the colon. Materials and Methods: Six patients with asymptomatic DD (ADD), 10 patients with symptomatic DD (SDD), and 11 healthy patients were used for the study. SDD sigmoid colon samples were collected from patients who underwent elective surgery. Specimens of healthy (control) and ADD-affected sigmoid colon were collected from patients operated on for non-obstructing colon tumours. Samples of the myenteric and submucosal plexuses with the surrounding tissue were observed with a transmission electron microscope. Results: Neurons in patients with SDD exhibited lamellar bodies and lipofuscin-like inclusions. Axons appeared fragmented, more swollen axons were found in the myenteric plexus of SDD samples (controls 6.9%, ADD 10.4%, SDD 13.3%, p=0.046). The mean area of healthy axon profiles was lower in asymptomatic patients (controls 0.69 µm2 , ADD 0.49 µm2 , SDD 0.71 µm2 , F=10.32, p<0.0001). The percentage of swollen axons (controls 4.3%, ADD 8.4%, SDD 9.8%, p=0.01) as well as the size of the axons (controls 0.66 µm2 , ADD 0.68 µm2, SDD 0.54 µm2 , F=3.50, p=0.03) in the submucosal plexus changed as well. Finally, mast cells were often found near nerves in the inner submucosal plexus. Conclusions: Diseased patients show ultrastructural alterations of the enteric nerve system (ENS). The morphometric data give evidence that the disease is associated with changes related to inflammation and remodeling. Further findings might prove important in understanding the disease.