The distributions of nerve fibres immunoreactive for the peptides calcitonin gene-related peptide (CGRP), enkephalin (ENK), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP), and vasoactive intestinal peptide (VIP) and the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) were studied in healthy colon and samples of ganglionic and aganglionic colon from cases of proven Hirschsprung's disease. Studies of coexistence of reactivities in nerve fibres were performed to predict the possible origins of fibres that are found in the aganglionic bowel, e. g., from sensory or sympathetic ganglia. The muscularis externa of the ganglionic colon contained many nerve fibres immunoreactive for ENK, SP, and VIP, fewer for NPY, and only rare fibres reactive for CGRP, SOM, or TH. In ganglionic colon reactivities for SP and ENK coexisted in nerve fibres in the muscularis externa but in aganglionic colon no ENK immunoreactivity was found and most SP fibres were double-labelled with CGRP reactivity, indicating their probable sensory nature. Abnormally increased numbers of somatostatin-reactive fibres and noradrenergic fibres (marked by TH) were noted in the external muscle, but no coexistence was seen between these reactivities and only a small proportion of the noradrenergic fibres in the muscle showed NPY reactivity although almost all around blood vessels did. Many fibres in the diseased segment had coexistence of NPY and VIP reactivities; these may arise from more orally located intrinsic cell bodies or from pelvic parasympathetic ganglia. In the mucosa of aganglionic colon there was a striking lack of SP-reactive fibres while other fibre types were often normal in number. It is concluded that nerve fibres from sensory ganglia, sympathetic ganglia, nerve cells located more oral in the ganglionated part, and possibly from pelvic parasympathetic ganglia invade the aganglionic bowel in Hirschsprung's disease.
- Hirschsprung's disease