Peptidergic innervation of the internal anal sphincter in Hirschsprung's disease

Abstract

The pathophysiology of the impaired sphincter function in Hirschsprung's disease is still unclear. The peptidergic innervation of the aganglionic large intestine is known to be disturbed. The present study analyzes the peptidergic innervation of the aganglionic internal anal sphincter (IAS) in comparison with that of the circular layer of ganglionic and aganglionic large intestine. Immunoreactivity for the following substances was analyzed: vasoactive intestinal polypeptide (VIP), substance P (SP), met-enkephalin (ENK), calcitonin gene-related peptide (CGRP), somatostatin (SOM), and neuropeptide Y (NPY). All patients were operated upon with Soave's endorectal pull-through technique and a posterior partial myectomy of the IAS. For comparison, specimens of resected IAS from adult patients operated upon for rectal cancer as well as autopsy specimens from a 2-year-old child were analyzed. Differences in the density of nerve fibers between the ganglionic and aganglionic large intestine were in accordance with previous studies. In sections of normoganglionic IAS moderately dense networks of nerve fibers immunoreactive for NPY, SOM, and VIP were observed. The occurrence of NPY and SOM was somewhat more frequent here compared to the colonic circular muscle coat, whereas the opposite was seen for VIP. In aganglionic IAS abundant nerve fibers immunoreactive for NPY, SOM, and VIP were observed. Only a few SP-, CGRP-, and ENK-immunoreactive fibers were found in normal and aganglionic IAS. It is concluded that there were moderate differences in the peptidergic innervation of the aganglionic IAS as compared to the normal ganglionic IAS and the circular muscle coat of the ganglionic and aganglionic large intestine.