Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation.

Background Chronic constipation ( CC) is a common and severe gastrointestinal complaint in Parkinson's disease ( PD), but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation ( PD/ CC) vs both CC and controls. Methods Twenty-nine PD/ CC and 10 Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched subjects served as controls. Colonic transit time measurement and conventional anorectal manometry were evaluated in PD/ CC and CC patients. Colonoscopy was performed in all three groups. Colonic submucosal whole mounts from PD/ CC, CC, and controls were processed for immunohistochemistry with antibodies for vasoactive intestinal polypeptide ( VIP) and peripheral choline acetyltransferase, markers for functionally distinct submucosal neurons. The mRNA expression of VIP and its receptors were also assessed. Key Results Four subgroups of PD/ CC patients were identified: delayed colonic transit plus altered anorectal manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%); and no transit and manometric impairment (9%). There were no differences in the number of neurons/ganglion between PD/ CC vs CC or vs controls. A reduced number of submucosal neurons containing VIP immunoreactivity was found in PD/ CC vs controls ( P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced in PD/ CC vs CC and controls ( P<.05). Conclusions and Inferences Colonic motor and rectal sensory functions are impaired in most PD/ CC patients. These abnormalities are associated with a decreased VIP expression in submucosal neurons. Both sensory-motor abnormalities and neurally mediated motor and secretory mechanisms are likely to contribute to PD/ CC pathophysiology. [ABSTRACT FROM AUTHOR]