Alterations in descending brain-spinal pathways regulating colorectal motility in a rat model of Parkinson's disease

Am J Physiol Gastrointest Liver Physiol. 2023 Dec 19. doi: 10.1152/ajpgi.00181.2023. Online ahead of print.ABSTRACTPatients with Parkinson's disease (PD) often have constipation. It is assumed that a disorder of the regulatory mechanism of colorectal motility by the central nervous system is involved in the constipation, but this remains unclear. The aim of this study was to investigate whether central neural pathways can modulate colorectal motility in a rat model of PD. PD model rats were generated by injection of 6-hydroxydopamine into a unilateral medial forebrain bundle and destruction of dopaminergic neurons in the substantia nigra. Colorectal motility was measured in vivo in anesthetized rats. Intraluminal administration of capsaicin, as a noxious stimulus, induced colorectal motility in sham rats but not in PD rats. Intrathecally administered dopamine (DA) and serotonin (5-HT), which mediate the prokinetic effect of capsaicin, at the L6-S1 levels enhanced colorectal motility in PD rats similarly to that in sham rats. In PD rats, capsaicin enhanced colorectal motility only when a GABAA receptor antagonist was pre-administered into the lumbosacral spinal cord. Capsaicin-induced colorectal motility was abolished by intrathecal administration of a D2-like receptor antagonist but not by administration of 5-HT2 and 5-HT3 receptor antagonists. These findings demonstrate that the inhibitory GABAergic component becomes operative and the stimulatory serotonergic component is su...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Source Type: research