Combined MRI, high-resolution manometry and a randomised trial of bisacodyl versus hyoscine show the significance of an enlarged colon in constipation: the RECLAIM study.

Background: Colonic motility in constipation can be assessed non-invasively using MRI.

Objective: To compare MRI with high-resolution colonic manometry (HRCM) for predicting treatment response.

Design: Part 1: 44 healthy volunteers (HVs), 43 patients with irritable bowel syndrome with constipation (IBS-C) and 37 with functional constipation (FC) completed stool diaries and questionnaires and underwent oral macrogol (500-1000 mL) challenge.

Novel insights into mechanisms of inhibition of colonic motility by loperamide.

Background: It is well known that opiates slow gastrointestinal (GI) transit, via suppression of enteric cholinergic neurotransmission throughout the GI tract, particularly the large intestine where constipation is commonly induced. It is not clear whether there is uniform suppression of enteric neurotransmission and colonic motility across the full length of the colon. Here, we investigated whether regional changes in colonic motility occur using the peripherally-restricted mu opioid agonist, loperamide to inhibit colonic motor complexes (CMCs) in isolated mouse colon.

TRPV4 is expressed by enteric glia and muscularis macrophages of the colon but does not play a prominent role in colonic motility.

Background: Mechanosensation is an important trigger of physiological processes in the gastrointestinal tract. Aberrant responses to mechanical input are associated with digestive disorders, including visceral hypersensitivity. Transient Receptor Potential Vanilloid 4 (TRPV4) is a mechanosensory ion channel with proposed roles in visceral afferent signaling, intestinal inflammation, and gut motility.

Types of Neurons in the Human Colonic Myenteric Plexus Identified by Multilayer Immunohistochemical Coding.

Background And Aims: Gut functions including motility, secretion, and blood flow are largely controlled by the enteric nervous system. Characterizing the different classes of enteric neurons in the human gut is an important step to understand how its circuitry is organized and how it is affected by disease.

Methods: Using multiplexed immunohistochemistry, 12 discriminating antisera were applied to distinguish different classes of myenteric neurons in the human colon (2596 neurons, 12 patients) according to their chemical coding.

Inhibited postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) have recurrent lower abdominal pain, associated with altered bowel habit (diarrhea and/or constipation). As bowel habit is altered, abnormalities in colonic motility are likely to contribute; however, characterization of colonic motor patterns in patients with IBS remains poor. Utilizing fiber-optic manometry, we aimed to characterize distal colonic postprandial colon motility in diarrhea-predominant IBS.

Analysis of Intestinal Movements with Spatiotemporal Maps: Beyond Anatomy and Physiology.

Over 150 years ago, methods for quantitative analysis of gastrointestinal motor patterns first appeared. Graphic representations of physiological variables were recorded with the kymograph after the mid-1800s. Changes in force or length of intestinal muscles could be quantified, however most recordings were limited to a single point along the digestive tract.

Impact of exercise duration on gastrointestinal function and symptoms.

The study aimed to determine the impact of exercise duration on gastrointestinal functional responses and gastrointestinal symptoms (GISs) in response to differing exercise durations. Endurance runners ( = 16) completed three trials on separate occasions, randomized to 1 h (1-H), 2 h (2-H), and 3 h (3-H) of running at 60% V̇o in temperate ambient temperature. Orocecal transit time (OCTT) was determined by lactulose challenge, with concomitant breath hydrogen (H) determination.

Does exertional heat stress impact gastrointestinal function and symptoms?

Objectives: Exertional-heat stress generates a thermoregulatory strain that exacerbates splanchnic hypoperfusion and sympathetic drive, but the effects on gastrointestinal function are poorly defined. The study aimed to determine the effects of exertional-heat stress on gastric myoelectrical activity, orocecal transit time (OCTT), and gastrointestinal symptoms (GIS).

Design: Randomised cross-over study.

Disengaging spinal afferent nerve communication with the brain in live mice.

Our understanding of how abdominal organs (like the gut) communicate with the brain, via sensory nerves, has been limited by a lack of techniques to selectively activate or inhibit populations of spinal primary afferent neurons within dorsal root ganglia (DRG), of live animals. We report a survival surgery technique in mice, where select DRG are surgically removed (unilaterally or bilaterally), without interfering with other sensory or motor nerves. Using this approach, pain responses evoked by rectal distension were abolished by bilateral lumbosacral L5-S1 DRG removal, but not thoracolumbar T13-L1 DRG removal.

The effects of loperamide on excitatory and inhibitory neuromuscular function in the human colon.

Background: In most animal species, opioids alter colonic motility via the inhibition of excitatory enteric motor neurons. The mechanisms by which opioids alter human colonic motility are unclear. The aim of this study was to describe the effects of loperamide on neuromuscular function in the human colon.

Abnormal Perception of Urge to Defecate: An Important Pathophysiological Mechanism in Women With Chronic Constipation.

Introduction: Although the association of absent or attenuated "call to stool" with constipation is well-recognized, no studies have systematically evaluated the perception of urge to defecate in a well-defined cohort of patients with chronic constipation (CC).

Methods: A prospective study of 43 healthy adult women and 140 consecutive adult women attending a tertiary center for investigation of CC. All participants completed a 5-day viscerosensory questionnaire, and all women with CC also underwent anorectal physiologic investigations.

Sympathetic Pathways Target Cholinergic Neurons in the Human Colonic Myenteric Plexus.

Background: The sympathetic nervous system inhibits human colonic motility largely by effects on enteric neurons. Noradrenergic axons, which branch extensively in the myenteric plexus, are integral to this modulatory role, but whether they contact specific types of enteric neurons is unknown. The purpose of this study was to determine the association of noradrenergic varicosities with types of enteric neurons.

Novel intrinsic neurogenic and myogenic mechanisms underlying the formation of faecal pellets along the large intestine of guinea-pigs.

Soft faecal material is transformed into discrete, pellet-shaped faeces at the colonic flexure. Here, analysis of water content in natural faecal material revealed a decline from cecum to rectum without significant changes at the flexure. Thus, pellet formation is not explained by changes in viscosity alone.

Long range synchronization within the enteric nervous system underlies propulsion along the large intestine in mice.

How the Enteric Nervous System (ENS) coordinates propulsion of content along the gastrointestinal (GI)-tract has been a major unresolved issue. We reveal a mechanism that explains how ENS activity underlies propulsion of content along the colon. We used a recently developed high-resolution video imaging approach with concurrent electrophysiological recordings from smooth muscle, during fluid propulsion.

Duodenal and proximal jejunal motility inhibition associated with bisacodyl-induced colonic high-amplitude propagating contractions.

Bisacodyl is a stimulant laxative often used in manometric studies of pediatric constipation to determine if it can initiate propulsive high-amplitude propagating contractions (HAPCs). Whereas the effects of bisacodyl infusion on colonic motility are well described, the effects of the drug on other regions of the gut after colonic infusion are not known. The aim of the present study was to characterize the effects of bisacodyl on both colonic and small bowel motility.

High-resolution impedance manometry characterizes the functional role of distal colonic motility in gas transit.

Background: The colonic motor patterns associated with gas transit are poorly understood. This study describes the application of high-resolution impedance manometry (HRiM) in the human colon in vivo to characterize distal colonic motility and gas transit; (a) after a meal and (b) after intraluminal gas insufflation into the sigmoid colon.

Methods: HRiM recordings were performed in 19 healthy volunteers, with sensors positioned from the distal descending colon to the proximal rectum.

Automated Analysis Using a Bayesian Functional Mixed-Effects Model With Gaussian Process Responses for Wavelet Spectra of Spatiotemporal Colonic Manometry Signals.

Manual analysis of human high-resolution colonic manometry data is time consuming, non-standardized and subject to laboratory bias. In this article we present a technique for spectral analysis and statistical inference of quasiperiodic spatiotemporal signals recorded during colonic manometry procedures. Spectral analysis is achieved by computing the continuous wavelet transform and cross-wavelet transform of these signals.

Motor patterns in the proximal and distal mouse colon which underlie formation and propulsion of feces.

Background: In herbivores, the proximal and distal colonic regions feature distinct motor patterns underlying formation and propulsion of fecal pellets, respectively. Omnivores, such as mice and humans, lack a similar clear anatomical transition between colonic regions. We investigated whether distinct processes form and propel content along the large intestine of a mouse (an omnivore).

Altered anal slow-wave pressure activity in low anterior resection syndrome: short case series in two independent specialist centres provide new mechanistic insights.

Aim: Conventional parameters (anal resting and squeeze pressures) measured with anorectal manometry (ARM) fail to identify anal sphincter dysfunction in many patients with low anterior resection syndrome (LARS). We aimed to assess whether there are differences in anal canal slow-wave pressure activity in LARS patients and healthy individuals.

Method: High-resolution ARM (HR-ARM) traces of 21 consecutive male LARS patients referred to the Royal London Hospital, UK (n = 12) and Aarhus University Hospital, Denmark (n = 9) were compared with HR-ARM data from 37 healthy men.

Identification of neurogenic intestinal motility patterns in silver perch (Bidyanus bidyanus) that persist over wide temperature ranges.

Background: Fish are increasingly being utilized as a model species for genetic manipulation studies related to gastrointestinal (GI) motility. Our aim was to identify whether patterns of GI motility in fish and the mechanisms underlying their generation are similar to those recorded from mammals (including humans).

Methods: The entire intestine was removed from euthanized adult Silver Perch (n = 11) and lesioned at the midway point to obtain two equal lengths.

Characterization of alternating neurogenic motor patterns in mouse colon.

Background: Colonic motor complexes (CMCs) have been widely recorded in the large intestine of vertebrates. We have investigated whether in the smooth muscle, a single unified pattern of electrical activity, or different patterns of electrical activity give rise to the different neurogenic patterns of motility underlying CMCs in vitro.

Methods: To study differences of the CMCs between proximal and distal colon, we used a novel combination of techniques to simultaneously record muscle diameter and force at multiple sites along the whole mouse colon ex vivo.

Coexistent faecal incontinence and constipation: A cross-sectional study of 4027 adults undergoing specialist assessment.

Background: In contrast to paediatric and geriatric populations, faecal incontinence and constipation in adults are generally considered separate entities. This may be incorrect.

Methods: Cross-sectional study of consecutive patients (18-80 years) referred to a tertiary unit (2004-2016) for investigation of refractory faecal incontinence and/or constipation and meeting Rome IV core criteria (applied post-hoc) for self-reported symptoms.

Effects of Lactate on One Class of Group III (CT3) Muscle Afferents.

A class of Group III muscle afferent neurons has branching sensory terminals in the connective tissue between layers of mouse abdominal muscles ("CT3 muscle afferents"). These sensory endings are both mechanosensitive and metabosensitive. In the present study, responses of CT3 afferents to lactate ions and changes in temperature were recorded.

A Novel Method for Electrophysiological Analysis of EMG Signals Using MesaClip.

In electrophysiology, many methods have been proposed for the analysis of action potential firing frequencies. The aim of this study was to present an algorithm developed for a continuous wavelet transform that enables the filtering out of frequencies contributing to the shapes of action potentials (spikes), whilst retaining the frequencies that encode the periodicity of spike trains. The continuous wavelet transform allows us to decompose a signal into its constituent frequencies.

Distinct patterns of myogenic motor activity identified in isolated human distal colon with high-resolution manometry.

Background: Colonic high-resolution manometry (HRM) has been used to reveal discrete, propagating colonic motor patterns. To help determine mechanisms underlying these patterns, we used HRM to record contractile activity in human distal colon ex vivo.

Methods: Surgically excised segments of descending (n = 30) or sigmoid colon (n = 4) were immersed in oxygenated Krebs solution at 36°C (n = 34; 16 female; 67.