Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associated with gas expulsion. Our hypothesis was that the SPW might be a critical component of most colonic motor functions, and hence might act as a biomarker for healthy colon motility. To that end, we performed high-resolution colonic manometry (HRCM), for the first time using an 84-sensor (1 cm spaced) water-perfused catheter, in 17 healthy volunteers. Intraluminal pressure patterns were recorded during baseline, proximal and rectal balloon distention, after a meal and following proximal and rectal luminal bisacodyl administration. Quantification was performed using software, based on Image J, developed during this study. Gas expulsion was always associated with SPWs, furthermore, SPWs were associated with water or balloon expulsion. SPWs were prominently emerging at the termination of proximal high amplitude propagating pressure waves (HAPWs); we termed this motor pattern HAPW-SPWs; hence, SPWs were often not a pan-colonic event. SPWs and HAPW-SPWs were observed at baseline with SPW amplitudes of 12.0 ± 8.5 mmHg and 20.2 ± 7.2 mmHg respectively. The SPW occurrence and amplitude significantly increased in response to meal, balloon distention and luminal bisacodyl, associated with 50.3% anal sphincter relaxation at baseline, which significantly increased to 59.0% after a meal, and 69.1% after bisacodyl. Often, full relaxation was achieved. The SPWs associated with gas expulsion had a significantly higher amplitude compared to SPWs without gas expulsion. SPWs could be seen to consist of clusters of high frequency pressure waves, likely associated with a cluster of fast propagating, circular muscle contractions. SPWs were occasionally observed in a highly rhythmic pattern at 1.8 ± 1.2 cycles/min. Unlike HAPWs, the SPWs did not obliterate haustral boundaries thereby explaining how gas can be expelled while solid content can remain restrained by the haustral boundaries. In conclusion, the SPW may become a biomarker for normal gas transit, the gastrocolonic reflex and extrinsic neural reflexes. The SPW assessment reveals coordination of activities in the colon, rectum and anal sphincters. SPWs may become of diagnostic value in patients with colonic dysmotility.

High-resolution colonic manometry and biopsy immunohistochemistry revealed that 5-HT4 receptors in the lumen of the human colon are present exclusively on enterochromaffin cells and the 5-HT4 receptor agonist prucalopride, evokes all major propulsive motor patterns, associated with significant anal sphincter relaxation, when given intraluminally.

Background: Luminal application of 5-HT ₄ receptor agonists can increase peristalsis in the guinea pig, mouse, rat and rabbit colon. Our aim in the present study was to test the effects of intraluminal prucalopride on motor patterns in the human colon. Methods: Colonic motor patterns were studied in vivo in a healthy volunteer using High-Resolution Colonic Manometry (HRCM) with an 84-sensor water perfused catheter with 1cm spacing. 5-HT and 5-HT ₄ receptor immunohistochemistry was performed on human tissue biopsies throughout the colon. Key results: Activating mucosal 5-HT ₄ receptors via intraluminal prucalopride enhanced propulsive motor activity in the human colon by increasing occurrence and amplitude of propulsive motor patterns including high-amplitude propagating pressure waves (HAPWs), pancolonic simultaneous pressure waves (SPWs) and HAPW-SPWs. Prucalopride-induced motor patterns had a close temporal association with a significant degree of anal sphincter relaxation and some were accompanied by a strong urge to defecate. Biopsies showed 100% colocalization of the 5-HT ₄ receptor to enterochromaffin cells throughout the colon and rectum. Conclusions and inferences: Activating luminal 5-HT ₄ receptors on enterochromaffin cells by intraluminal prucalopride increased propulsive motor activity. 5-HT ₄ receptors were found only on enterochromaffin cells and not ubiquitous on all epithelial cells. Our data support incorporation of prucalopride in colon-specific drug delivery systems as a prokinetic to treat colonic hypomotility disorders. 50 word High-resolution colonic manometry and biopsy immunohistochemistry revealed that 5-HT ₄ receptors in the lumen of the human colon are present exclusively on enterochromaffin cells and that the 5-HT ₄ agonist prucalopride evokes all major propulsive motor patterns, associated with significant anal sphincter relaxation, when given intraluminally. 250-character clinical message: Activating luminal 5-HT ₄ receptors on enterochromaffin cells by intraluminal prucalopride increased propulsive motor activity in the human colon. Colon-specific delivery systems with a 5-HT ₄ agonist may become the preferred colon prokinetic.