Dopaminergic defect of enteric nervous system in Parkinsonʹs disease patients with chronic constipation

Clinical studies suggest that gut disorders are common in Parkinsonʹs disease, but the morphological basis is unknown. Depletion of dopamine-containing neurons in the central nervous system is a basic defect in Parkinsonʹs disease. We compared colonic tissue from 11 patients with advanced Parkinsonʹs disease, 17 with adenocarcinoma (normal tissue was studied), and five who underwent colectomy for severe constipation. Immunohistochemistry was used to stain myenteric and submucosal neurons for dopamine, tyrosine hydroxylase, and vasoactive intestinal polypeptide (VIP). Each class of neurons was quantified as a percentage of the total neuronal population stained for the marker protein gene product 9·5. Nine of the 11 Parkinsonʹs disease patients had substantially fewer dopaminergic myenteric neurons than the other subjects (mean 0·4 [SE 0·2] vs 6·9 [2·3] in controls and 5·7 [2·0] in constipated subjects). There was very little difference between the groups in numbers of tyrosine-hydroxylase and VIP neurons. Two Parkinsonʹs disease patients had similar distributions of all types of neurons, including dopaminergic myenteric neurons, to the controls. High-performance liquid chromatography showed lower levels of dopamine in the muscularis externa (but not mucosa) in four Parkinsonʹs disease patients than in four controls (7·3 [5·1] vs 24·2 [4·6] nmol per g protein), but levels of dopamine metabolites were similar in the two groups. The identification of this defect of dopaminergic neurons in the enteric nervous system in Parkinsonʹs disease may lead to better treatment of colorectal dysfunction in this disease.