The proximal colonic motor response to rectal mechanical and chemical stimulation

Abstract

We aimed to determine whether rectal distension and/or infusion of bile acids stimulates propagating or nonpropagating activity in the unprepared proximal colon in 10 healthy volunteers using a nasocolonic manometric catheter (16 recording sites at 7.5-cm spacing). Sensory thresholds and proximal colonic motor responses were assessed following rectal distension by balloon inflation and rectal instillation of chenodeoxycholic acid. Maximum tolerated balloon volume and the volume that stimulated a desire to defecate were both significantly (P < 0.01) reduced after rectal chenodeoxycholic acid. The frequency of colonic propagating pressure wave sequences decreased significantly in response to initial balloon inflations (P < 0.05), but the frequency doubled after subsequent chenodeoxycholic acid infusion (P < 0.002). Nonpropagating activity decreased after balloon inflation, was not influenced by acid infusion, and demonstrated a further decrease in response to repeat balloon inflation. We concluded that rectal chenodeoxycholic acid in physiological concentrations is a potent stimulus for propagating pressure waves arising in the proximal colon and reduces rectal sensory thresholds. Rectal distension inhibits all colonic motor activity.

Relamorelin to Treat Constipation: “Pusher” or Pushover?

“…All in all, the available literature and those provided in the study suggest that since relamorelin might be considered as a relatively pure ''pusher,'' at least in the colon, this drug may be effective in the treatment of constipation, even though its propulsive effects seem to be relatively feeble when compared with those characteristic of other drugs [5][6][7][8]. Nevertheless, its ability to stimulate proximal gut motility [11] combined with its subcutaneous route of administration might benefit not only conventional constipated subjects, but also other subtypes of constipation such as in post-operative and neutrally compromised patients, and in patients refractory to all other medications [13].…”

“…Therefore, since drugs can increase the frequency and amplitude of colonic contractions, especially the manometric equivalents of mass movements, termed high-amplitude propagated contractions [4], such medications could prove useful tools in constipation treatment. To date, objective documentation in humans of such stimulation is available for only a few clinically available drugs, including bisacodyl [5], macrogol [6], chenodeoxycholic acid [7], and prucalopride [8].…”

“…Caution should, however, be the rule when interpretating such data, since some of these studies have been conducted only in healthy volunteers [6][7][8], and at least for one of them the findings have not been reproduced in either controls or patients [9]; therefore, further data, possibly obtained in patients with chronic constipation, would be indeed welcome.…”

Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists

“…The observed activity in the colon is comparable to the effects seen following a treatment with other colonic prokinetics such as prucalopride, or other serotonin receptor agonists or neostigmine; however, in contrast to the above mentioned drugs RM-131 exhibits a delayed effect (24-36 hour postadministration) on the colonic motility. [42][43][44] To further characterize the effects reported in the human colon the same group of authors evaluated the clinical efficacy of RM-131 in patients with confirmed CC. Similarly to their first clinical trial, the propulsive effects of RM-131 were confirmed, and the trial added that the duration of RM-131 is long-lasting with RM-131 activity being reported for a minimum of 1 hour.…”

Modular and functionally-different descending recto-anal motor pathways in a rat model

“…Functionally-different recto-anal excitatory [5] or inhibitory reflex pathways [3,[6][7][8], as well as rectocolonic inhibitory [9] and colorectal stimulatory [10] reflex pathways, have been demonstrated in the mammalian rectum. The recto-anal function in the discrimination of gut content is mainly attributed to the enteric recto-anal reflex, which consists of rectal contraction and the internal relaxation of the anal sphincter.…”