Hirschsprung's disease: absence of serotonergic neurons in the aganglionic colon

The distribution of enteric serotonergic neurons was studied in patients with Hirschsprung's disease. Specimens of bowel obtained at surgery were incubated in vitro with tritiated serotonin (3H-5-HT) in the presence of a high concentration of nonradioactive norepinephrine. Sites of high-affinity 3H-5-HT uptake were visualized by light-microscopic autoradiography. Specimens taken from ganglionic regions of the intestine (distal ileum or colon) showed intense labeling of the neuropil within the myenteric plexus. Silver grains were localized in a pericellular distribution around ganglion cells, but the ganglion cells themselves were relatively free of overlying silver grains. Corresponding regions of aganglionic colon or rectum demonstrated silver grain densities equivalent to background levels. Specific labeling was absent over the large nerve trunks in this region. These results suggest that 5-HT-containing neurons are present in the normal human intestine and that these neurons are absent in the aganglionic segment in Hirshsprung's disease.