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Motor function of the colon is essential for health. Our current understanding of the mechanisms that underlie colonic motility are based upon a range of experimental techniques, including molecular biology, single cell studies, recordings from muscle strips, analysis of part or whole organ ex vivo through to in vivo human recordings. For the surgeon involved in the clinical management of colonic conditions this amounts to a formidable volume of material. Here, we synthesize the key findings from these various experimental approaches so that surgeons can be better armed to deal with the complexities of the colon., (© 2023 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Indirect immunofluorescence is usually restricted to 3-5 markers per preparation, limiting analysis of coexistence. A solution containing 2-mercaptoethanol and sodium dodecyl sulfate (2-ME/SDS) can elute indirect immunofluorescence labelling (i.e. primary antisera followed by fluorophore-conjugated secondary antisera) and has been used for sequential staining of sections. The aim of this study was to test whether 2-ME/SDS is effective for eluting indirect immunofluorescent staining (with primary antisera visualised by fluorophore-coupled secondary antisera) in wholemount preparations. We also analysed how 2-ME/SDS may work and used this understanding to devise additional uses for immunofluorescence in the nervous system. 2-ME/SDS appears to denature unfixed proteins (including antisera used as reagents) but has much less effect on antigenicity of formaldehyde-fixed epitopes. Moieties linked by strong biotin-streptavidin bonds are highly resistant to elution by 2-ME/SDS. Two primary antisera raised in the same species can be applied without spurious cross-reactivity, if a specific order of labelling is followed. The first primary antiserum is followed by a biotinylated secondary, then a tertiary of fluorophore-conjugated streptavidin. The preparation is then exposed to 2-ME/SDS, which has minimal impact on labelling by the first primary/secondary/tertiary combination. However, when this is followed by a second primary antiserum (raised in the same species), followed by a fluorophore-conjugated secondary antiserum, the intervening 2-ME/SDS exposure prevents cross-reactivity between primary and secondary antisera of the two layers. A third property of 2-ME/SDS is that it reduces lipofuscin autofluorescence, although it also raises background fluorescence and strongly enhances autofluorescence of erythrocytes. In summary, 2-ME/SDS is easy to use, cost-effective and does not require modified primary antisera. It can be used as the basis of a multi-layer immunohistochemistry protocol and allows 2 primary antisera raised in the same species to be used together., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Aims: Viscerofugal neurons (VFNs) have cell bodies in the myenteric plexus and axons that project to sympathetic prevertebral ganglia. In animals they activate sympathetic motility reflexes and may modulate glucose metabolism and feeding. We used rapid retrograde tracing from colonic nerves to identify VFNs in human colon for the first time, using ex vivo preparations with multi-layer immunohistochemistry., Methods: Colonic nerves were identified in isolated preparations of human colon and set up for axonal tracing with biotinamide. After fixation, labeled VFN cell bodies were subjected to multiplexed immunohistochemistry for 12 established nerve cell body markers., Results: Biotinamide tracing filled 903 viscerofugal nerve cell bodies ( n = 23), most of which (85%) had axons projecting orally before entering colonic nerves. Morphologically, 97% of VFNs were uni-axonal. Of 215 VFNs studied in detail, 89% expressed ChAT, 13% NOS, 13% calbindin, 9% enkephalin, 7% substance P and 0 of 123 VFNs expressed CART. Few VFNs contained calretinin, VIP, 5HT, CGRP, or NPY. VFNs were often surrounded by dense baskets of axonal varicosities, probably reflecting patterns of connectivity; VAChT+ (cholinergic), SP+ and ENK+ varicosities were most abundant around them. Human VFNs were diverse; showing 27 combinations of immunohistochemical markers, 4 morphological types and a wide range of cell body sizes. However, 69% showed chemical coding, axonal projections, soma-dendritic morphology and connectivity similar to enteric excitatory motor neurons., Conclusion: Viscerofugal neurons are present in human colon and show very diverse combinations of features. High proportions express ChAT, consistent with cholinergic synaptic outputs onto postganglionic sympathetic neurons in prevertebral ganglia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Chen, Humenick, Hibberd, Yew, Wattchow, Dinning, Costa, Spencer and Brookes.)

Background: Simultaneous pressure waves (SPW) spanning all recording sites in colonic manometry studies have been described as a potential biomarker of normal gas transit and extrinsic neural reflexes. In pediatric studies utilizing combined antroduodenal and colonic manometry, it was noted that most colonic SPWs appeared to also span all sensors in the gastric and small bowel regions. This suggests that a proportion of colonic SPWs may represent an artefact caused by forces extrinsic to the colon. Our aim was to characterize colonic SPWs and determine how many of these spanned most of the digestive tract., Methods: In 39 combined high-resolution antroduodenal and colonic manometry traces from 27 pediatric patients, we used our purpose-built software to identify all SPWs that spanned either (i) all recording sites in the digestive tract or (ii) those restricted to the colon., Results: A total of 14,565 SPWs were identified (364 ± 316 SPWs/study), with 14,550 (99.9%) spanning the entire antroduodenal and colonic recording sites. Only 15 SPWs (0.1% of the total) were restricted to the colon (all in one recording)., Conclusions: Based on these findings, we suggest that, in pediatric studies, SPWs should not form part of any diagnostic criteria, as these events appear to be an artefact caused by factors outside the colon (abdominal strain, body motion).

A rhythmic expression of clock genes occurs within the cells of multiple organs and tissues throughout the body, termed "peripheral clocks." Peripheral clocks are subject to entrainment by a multitude of factors, many of which are directly or indirectly controlled by the light-entrainable clock located in the suprachiasmatic nucleus of the hypothalamus. Peripheral clocks occur in the gastrointestinal tract, notably the epithelia whose functions include regulation of absorption, permeability, and secretion of hormones; and in the myenteric plexus, which is the intrinsic neural network principally responsible for the coordination of muscular activity in the gut. This review focuses on the physiological circadian variation of major colonic functions and their entraining mechanisms, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. Pathophysiological states such as irritable bowel syndrome and ulcerative colitis and their interactions with circadian rhythmicity are also described. Finally, the classic circadian hormone melatonin is discussed, which is expressed in the gut in greater quantities than the pineal gland, and whose exogenous use has been of therapeutic interest in treating colonic pathophysiological states, including those exacerbated by chronic circadian disruption., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hibberd, Ramsay, Spencer-Merris, Dinning, Zagorodnyuk and Spencer.)

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. After an overnight fast, a 72-sensor (spaced at 1-cm intervals) manometry catheter was colonoscopically placed to the proximal colon, in 13 patients with IBS-D and 12 healthy adults. Recordings were taken for 2 h pre and post a 700 kcal meal. Data were analyzed with our two developed automated techniques. In both healthy adults and patients with IBS-D, the dominant frequencies of pressure waves throughout the colon are between 2 and 4 cycles per minute (cpm) and the power of these frequencies increased significantly after a meal. Although these pressure waves formed propagating contractions in both groups, the postprandial propagating contraction increase was significantly smaller in patients compared with healthy adults. In healthy adults during the meal period, retrograde propagation between 2 and 8 cpm was significantly greater than antegrade propagation at the same frequencies. This difference was not observed in IBS-D. Patients with IBS-D show reduced prevalence of the retrograde cyclic motor pattern postprandially compared with the marked prevalence in healthy adults. We hypothesize that this reduction may allow premature rectal filling, leading to postprandial urgency and diarrhea. NEW & NOTEWORTHY Compared with healthy adults this study has shown a significant reduction in the prevalence of the postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. We hypothesize that this altered motility may allow for premature rectal filling which contributes to the postprandial urgency and diarrhea experienced by these patients.

Purpose: The majority of patients with an anorectal malformation (ARM) have associated congenital anomalies. It is well established that all patients diagnosed with an ARM should undergo systematic screening, including renal, spinal, and cardiac imaging. This study aimed to evaluate the findings and completeness of screening, following local implementation of standardized protocols., Methods: A retrospective cohort study was performed assessing all patients with an ARM managed at our tertiary pediatric surgical center, following a standardized protocol implementation for VACTERL screening (January 2016-December 2021). Cohort demographics, medical characteristics, and screening investigations were analyzed. Findings were compared with our previously published data (2000-2015), conducted prior to protocol implementation., Results: One hundred twenty-seven (64 male, 50.4%) children were eligible for inclusion. Complete screening was performed in 107/127 (84.3%) children. Of these, one or more associated anomalies were diagnosed in 85/107 (79.4%), whilst the VACTERL association was demonstrated in 57/107 (53.3%). The proportion of children that underwent complete screening increased significantly in comparison with those assessed prior to protocol implementation (RR 0.43 [CI 0.27-0.66]; p < 0.001). Children with less complex ARM types were significantly less likely to receive complete screening (p = 0.028). Neither presence of an associated anomaly, nor prevalence of the VACTERL association, differed significantly by ARM type complexity., Conclusion: Screening for associated VACTERL anomalies in children with ARM was significantly improved following standardized protocol implementation. The prevalence of associated anomalies in our cohort supports the value of routine VACTERL screening in all children with ARM, regardless of malformation type., Level of Evidence: II., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Ondansetron may be beneficial in irritable bowel syndrome with diarrhoea (IBS-D)., Aim: To conduct a 12-week parallel group, randomised, double-blind, placebo-controlled trial of ondansetron 4 mg o.d. (titrated up to 8 mg t.d.s.) in 400 IBS-D patients., Primary Endpoint: % responders using the Food and Drug Administration (FDA) composite endpoint. Secondary and mechanistic endpoints included stool consistency (Bristol Stool Form Scale) and whole gut transit time (WGTT). After literature review, results were pooled with other placebo-controlled trials in a meta-analysis to estimate relative risks (RR), 95% confidence intervals (CIs) and number needed to treat (NNT)., Results: Eighty patients were randomised. On intention-to-treat analysis, 15/37 (40.5%; 95% CI 24.7%-56.4%) met the primary endpoint on ondansetron versus 12/43 (27.9%; 95% CI 14.5%-41.3%) on placebo (p = 0.19). Ondansetron improved stool consistency compared with placebo (adjusted mean difference - 0.7; 95% CI -1.0 to-0.3, p < 0.001). Ondansetron increased WGTT between baseline and week 12 (mean (SD) difference 3.8 (9.1) hours, versus placebo -2.2 (10.3) hours, p = 0.01). Meta-analysis of 327 patients from this, and two similar trials, demonstrated ondansetron was superior to placebo for the FDA composite endpoint (RR of symptoms not responding = 0.86; 95% CI 0.75-0.98, NNT = 9) and stool response (RR = 0.65; 95% CI 0.52-0.82, NNT = 5), but not abdominal pain response (RR = 0.95; 95% CI 0.74-1.20)., Conclusions: Although small numbers meant the primary endpoint was not met in this trial, when pooled with other similar trials meta-analysis suggests ondansetron improves stool consistency and reduces days with loose stool and urgency. Trial registration - http://www.isrctn.com/ISRCTN17508514., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Ex vivo intracellular recordings and dye fills, combined with immunohistochemistry, are a powerful way to analyze the enteric nervous system of laboratory animals., Methods: Myenteric neurons were recorded in isolated specimens of human colon. A key determinant of successful recording was near-complete removal of circular muscle from the surface of ganglia., Key Results: Treatment with a collagenase/neutral protease mix before dissection significantly improved recording success and reduced damage to the plexus. Carboxyfluorescein in microelectrodes allowed recorded neurons to be routinely labeled, analyzed, and subjected to multi-layer immunohistochemistry. Carboxyfluorescein revealed morphological details that were not detected by immunohistochemical methods. Of 54 dye-filled myenteric neurons (n = 22), 45 were uni-axonal and eight were multi-axonal. There was a significant bias toward recordings from large neural somata. The close association between morphology and electrophysiology (long after-hyperpolarizations and fast EPSPs) seen in mice and guinea pigs did not hold for human myenteric neuron recordings. No slow EPSPs were recorded; however, disruption to the myenteric plexus during dissection may have led the proportion of cells receiving synaptic potentials to be underestimated. Neurons immunoreactive for nitric oxide synthase were more excitable than non-immunoreactive neurons. Distinctive grooves were observed on the serosal and/or mucosal faces of myenteric neurons in 3D reconstructions. These had varicose axons running through them and may represent a preferential site of synaptic inputs., Conclusions: Human enteric neurons share many features with laboratory animals, but the combinations of features in individual cells appear more variable., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Despite surgical correction, children with anorectal malformations may experience long-term bowel dysfunction, including fecal incontinence and/or disorders of evacuation. Anorectal manometry is the most widely used test of anorectal function. Although considerable attention has been devoted to its application in the anorectal malformation cohort, there have been few attempts to consolidate the findings obtained. This systematic review aimed to (1) synthesize and evaluate the existing data regarding anorectal manometry results in children following anorectal malformation repair, and (2) evaluate the manometry protocols utilized, including equipment, assessment approach, and interpretation. We reviewed four databases (Embase, MEDLINE, the Cochrane Library, and PubMed) for relevant articles published between 1 January 1985 and 10 March 2022. Studies reporting post-operative anorectal manometry in children (<18 years) following anorectal malformation repair were evaluated for eligibility. Sixty-three studies were eligible for inclusion. Of the combined total cohort of 2155 patients, anorectal manometry results were reported for 1755 children following repair of anorectal malformations. Reduced resting pressure was consistently identified in children with anorectal malformations, particularly in those with more complex malformation types and/or fecal incontinence. Significant variability was identified in relation to manometry equipment, protocols, and interpretation. Few studies provided adequate cohort medical characteristics to facilitate interpretation of anorectal manometry findings within the context of the broader continence mechanism. This review highlights a widespread lack of standardization in the anorectal manometry procedure used to assess anorectal function in children following anorectal malformation repair. Consequently, interpretation and comparison of findings, both within and between institutions, is exceedingly challenging, if not impossible. Standardized manometry protocols, accompanied by a consistent approach to analysis, including definitions of normality and abnormality, are essential to enhance the comparability and clinical relevance of results.

The speed of pellet propulsion through the isolated guinea pig distal colon in vitro significantly exceeds in vivo measurements, suggesting a role for inhibitory mechanisms from sources outside the gut. The aim of this study was to investigate the effects of sympathetic nerve stimulation on three different neurogenic motor behaviors of the distal colon: transient neural events (TNEs), colonic motor complexes (CMCs), and pellet propulsion. To do this, segments of guinea pig distal colon with intact connections to the inferior mesenteric ganglion (IMG) were set up in organ baths allowing for simultaneous extracellular suction electrode recordings from smooth muscle, video recordings for diameter mapping, and intraluminal manometry. Electrical stimulation (1-20 Hz) of colonic nerves surrounding the inferior mesenteric artery caused a statistically significant, frequency-dependent inhibition of TNEs, as well as single pellet propulsion, from frequencies of 5 Hz and greater. Significant inhibition of CMCs required stimulation frequencies of 10 Hz and greater. Phentolamine (3.6 μM) abolished effects of colonic nerve stimulation, consistent with a sympathetic noradrenergic mechanism. Sympathetic inhibition was constrained to regions with intact extrinsic nerve pathways, allowing normal motor behaviors to continue without modulation in adjacent extrinsically denervated regions of the same colonic segments. The results demonstrate differential sensitivities to sympathetic input among distinct neurogenic motor behaviors of the colon. Together with findings indicating CMCs activate colo-colonic sympathetic reflexes through the IMG, these results raise the possibility that CMCs may paradoxically facilitate suppression of pellet movement in vivo, through peripheral sympathetic reflex circuits., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

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 ( n = 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 2max in temperate ambient temperature. Orocecal transit time (OCTT) was determined by lactulose challenge, with concomitant breath hydrogen (H 2 ) determination. Gastric slow wave activity was recorded using cutaneous electrogastrography (cEGG) before and after exertion. GIS was determined using a modified visual analog scale (mVAS). OCTT response was classified as very slow on all trials (∼93-101 min) with no trial difference observed ( P = 0.895). Bradygastria increased postexercise on all trials (means ± SD: 1-H: 10.9 ± 11.7%, 2-H: 6.2 ± 9.8%, and 3-H: 13.2 ± 21.4%; P < 0.05). A reduction in the normal gastric slow wave activity (2-4 cycles/min) was observed postexercise on 1-H only (-10.8 ± 17.6%; P = 0.039). GIS incidence and gut discomfort was higher on 2-H (81% and 12 counts) and 3-H (81% and 18 counts), compared with 1-H (69% and 6 counts) ( P = 0.038 and P = 0.006, respectively). Severity of gut discomfort, total-GIS, upper-GIS, and lower-GIS increased during exercise on all trials ( P < 0.05). Steady-state exercise in temperate ambient conditions for 1 h, 2 h, and 3 h instigates perturbations in gastric slow wave activity compared with rest and hampers OCTT, potentially explaining the incidence and severity on exercise-associated GIS. NEW & NOTEWORTHY Exercise stress per se appears to instigate perturbations to gastric myoelectrical activity, resulting in an increase in bradygastria frequency, inferring a reduction in gastric motility. The perturbations to gastrointestinal functional responses instigated by exercise per se, likely contribute to the high incidence and severity level of exercise-associated gastrointestinal symptoms. Cutaneous electrogastrography is not commonly used in exercise gastroenterology research, however, may be a useful aid in providing an overall depiction of gastrointestinal function. Particularly relating to gastrointestinal motility and concerning gastroparesis.

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. All antisera were applied to every neuron, in multiple layers, separated by elutions., Results: A total of 164 combinations of immunohistochemical markers were present among the 2596 neurons, which could be divided into 20 classes, with statistical validation. Putative functions were ascribed for 4 classes of putative excitatory motor neurons (EMN1-4), 4 inhibitory motor neurons (IMN1-4), 3 ascending interneurons (AIN1-3), 6 descending interneurons (DIN1-6), 2 classes of multiaxonal sensory neurons (SN1-2), and a small, miscellaneous group (1.8% of total). Soma-dendritic morphology was analyzed, revealing 5 common shapes distributed differentially between the 20 classes. Distinctive baskets of axonal varicosities surrounded 45% of myenteric nerve cell bodies and were associated with close appositions, suggesting possible connectivity. Baskets of cholinergic terminals and several other types of baskets selectively targeted ascending interneurons and excitatory motor neurons but were significantly sparser around inhibitory motor neurons., Conclusions: Using a simple immunohistochemical method, human myenteric neurons were shown to comprise multiple classes based on chemical coding and morphology and dense clusters of axonal varicosities were selectively associated with some classes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Children with anorectal malformations may experience constipation and fecal incontinence following repair. The contribution of altered anorectal function to these persistent symptoms is relatively intuitive; however, colonic motility in this cohort is less well understood. Manometry may be used to directly assess colonic motility., Purpose: The purpose of this systematic review was to synthesize the available evidence regarding post-operative colonic motility in children with anorectal malformations and evaluate the reported equipment and protocols used to perform colonic manometry in this cohort. This systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We conducted a systematic review of four databases: Embase, MEDLINE, PubMed, and the Cochrane Library (1 st January 1985-22 nd July 2021). Studies reporting colonic manometry performed in children following anorectal malformation repair were assessed for eligibility. Data were extracted independently by two authors. Four studies were eligible for inclusion. Of the combined total cohort of 151 children, post-operative colonic manometry was conducted in 35. Insufficient reporting of medical characteristics, bowel function, and manometric outcomes restricted comparison between studies, and limited clinical applicability. No results from high-resolution colonic manometry were identified. Despite the prevalence of post-operative bowel dysfunction in children with repaired anorectal malformations, this systematic review highlighted the markedly limited evidence regarding post-operative colonic motility. This cohort may benefit from assessment with high-resolution techniques; however, future work must emphasize adherence to standardized manometry protocols, and include robust reporting of surgical characteristics, bowel function, and manometric outcomes., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: In the human large bowel, sacral parasympathetic nerves arise from S2 to S4, project to the pelvic plexus ("hypogastric plexus") and have post-ganglionic axons entering the large bowel near the rectosigmoid junction. They then run long distances orally or aborally within the bowel wall forming "ascending nerves" or "shunt fascicles" running in the plane of the myenteric plexus. They form bundles of nerve fibres that can be distinguished from the myenteric plexus by their straight orientation, tendency not to merge with myenteric ganglia and greater width., Aim: To identify reliable marker(s) to distinguish these bundles of ascending nerves from other extrinsic and intrinsic nerves in human colon., Methods: Human colonic segments were obtained with informed consent, from adult patients undergoing elective surgery ( n = 21). Multi-layer immunohistochemical labelling with neurofilament-H (NF200), myelin basic protein (MBP), von Willebrand factor (vWF), and glucose transporter 1 (GLUT1), and rapid anterograde tracing with biotinamide, were used to compare ascending nerves and lumbar colonic nerves., Results: The rectosigmoid and rectal specimens had 6-11 ascending nerves spaced around their circumference. Distal colon specimens typically had 1-3 ascending nerves, with one located near the mesenteric taenia coli. No ascending nerves were observed in ascending colon specimens. GLUT1 antisera labelled both sympathetic lumbar colonic nerves and ascending nerves in the gut wall. Lumbar colonic nerves joined the myenteric plexus and quickly lost GLUT1 labelling, whereas GLUT1 staining labelled parasympathetic ascending nerves over many centimetres., Conclusion: Ascending nerves can be distinguished in the colorectum of humans using GLUT1 labelling combined with NF200., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Johnson, Humenick, Peterson, Costa, Wattchow, Sia, Dinning and Brookes.)

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., Methods: Tissue specimens of human colon from 10 patients undergoing an anterior resection were divided into three inter-taenial circular muscle strips. Separate organ baths were used to assess: (1) excitatory transmission (selective blockade of inhibitory transmission: L-NOARG/MRS2179); (2) inhibitory transmission (selective blockade of excitatory transmission: hyoscine hydrobromide); and (3) a control bath (no drug additions). Neuromuscular function was assessed using force transducer recordings and electrical field stimulation (EFS; 20 V, 10 Hz, 0.5 ms, 10 s) prior to and following loperamide and naloxone., Key Results: In human preparations with L-NOARG/MRS2179, loperamide had no significant effects on isometric contractions. In preparations with hyoscine hydrobromide, loperamide reduced isometric relaxation during EFS (median difference + 0.60 g post-loperamide, Z = -2.35, p = 0.019)., Conclusions and Inferences: Loperamide had no effect on excitatory neuromuscular function in human colonic circular muscle. These findings suggest that loperamide alters colonic function by acting primarily on inhibitory motor neurons, premotor enteric neurons, or via alternative non-opioid receptor pathways., (© 2022 John Wiley & Sons Ltd.)

Colonic motor complexes (CMCs) are a major neurogenic activity in guineapig distal colon. The identity of the enteric neurons that initiate this activity is not established. Specialized intrinsic primary afferent neurons (IPANs) are a major candidate. We aimed to test this hypothesis. To do this, segments of guineapig distal colon were suspended vertically in heated organ baths and propulsive forces acting on a pellet inside the lumen were recorded by isometric force transducer while pharmacological agents were applied to affect IPAN function. In the absence of drugs, CMCs acted periodically on the pellet, generating peak propulsive forces of 12.7 ± 5 g at 0.56 ± 0.22 cpm, lasting 49 ± 17 s (215 preparations; n = 60). Most but not all CMCs were abolished by nicotinic receptor blockade to inhibit fast excitatory synaptic transmission (50/62 preparations; n = 25). Remarkably, CMCs inhibited by hexamethonium were restored by a pharmacological strategy that aimed to enhance IPAN excitability. Thus, CMCs were restored by increased smooth muscle tension (using BAY K8644, bethanechol or carbachol) and by IPAN excitation using phorbol dibutyrate; NK3 receptor agonist, senktide; and partially by αCGRP. The IPAN inhibitor, 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazole-2-one (DCEBIO), decreased CMC frequency. CGRP, but not NK3-receptor antagonists, decreased CMC frequency in naive preparations. Finally, CMCs were blocked by tetrodotoxin, and this was not reversed by any drugs listed above. These results support a major role for IPANs that does not require fast synaptic transmission, in the periodic initiation of neurogenic propulsive contractions. Endogenous CGRP plays a role in determining CMC frequency, whereas further unidentified signaling pathways may determine their amplitude and duration. NEW & NOTEWORTHY The colonic motor complex (CMC) initiates propulsion in guinea pig colon. Here, CMCs evoked by an intraluminal pellet were restored during nicotinic receptor blockade by pharmacological agents that directly or indirectly enhance intrinsic primary afferent neuron (IPAN) excitability. IPANs are the only enteric neuron in colon that contain CGRP. Blocking CGRP receptors decreased CMC frequency, implicating their role in CMC initiation. The results support a role for IPANs in the initiation of CMCs.

Background: Hirschsprung disease is commonly encountered by pediatric surgeons. Despite advances in the surgical management, these children may experience symptoms of bowel dysfunction throughout adulthood. Anorectal manometry may be used to assess post-operative anorectal structure and function. This review aimed to consolidate and evaluate the literature pertaining to post-operative findings of anorectal manometry in children with Hirschsprung disease., Purpose: (1) Synthesize the available data regarding anorectal motility patterns in children following repair of Hirschsprung disease. (2) Evaluate the reported anorectal manometry protocols., Data Sources: We performed a systematic review of four databases: Embase, MEDLINE, the Cochrane Library, and PubMed., Study Selection: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting results of post-operative anorectal manometry in children with Hirschsprung disease were evaluated for inclusion., Results: Twenty-three studies satisfied inclusion criteria, with a combined cohort of 939 patients. Post-operative anorectal manometry results were reported for 682 children. The majority of included studies were assessed as "poor quality." Disparate manometry protocols, heterogeneous cohorts, and lack of standardized outcome assessments introduced a risk of outcome reporting bias, limited the comparability of results, and impeded clinical translation of findings., Conclusions: This systematic review demonstrated the lack of high-quality evidence underlying the current understanding of post-operative anorectal motility in children with HD. There was little consistency in reported manometry outcomes between studies. In future work, emphasis must be placed on the application of standardized manometry protocols, cohort reporting, and patient outcome assessments., (© 2021 John Wiley & Sons Ltd.)

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. Normal urge perception and abnormal urge perception were defined using a Naive Bayes model trained in healthy women (95% having normal urge)., Results: In total, 181 toilet visits in healthy women and 595 in women with CC were analyzed. Abnormal urge perception occurred in 70 (50.0%) women with CC. In this group, the urge to defecate was more often experienced as abdominal sensation (69.3% vs 41.4%; P < 0.0001), and the viscerosensory referral area was 81% larger (median pixels anterior: 1,849 vs 1,022; P < 0.0001) compared to women with CC and normal urge perception. Abnormal (vs normal) urge in women with CC was associated with more severe constipation (Cleveland Clinic constipation score: 19 vs 15 P < 0.0001), irritable bowel syndrome (45.7% vs 22.9% P < 0.0001), and a functional evacuation disorder on defecography (31.3% vs 14.3% P = 0.023). A distinct pattern of abnormal urge was found in women with CC and rectal hyposensitivity., Discussion: Abnormal urge perception was observed in 50% of women with CC and was frequently described as abdominal sensation, supporting the concept that sensory dysfunction makes an important contribution to the pathophysiology of constipation., (Copyright © 2022 by The American College of Gastroenterology.)

Background: There are considerable advantages and opportunities for surgeons and trainee surgeons in conducting a period of research allied with basic scientists. Such clinicians are well placed to define relevant clinical questions, provide human material (tissue, biopsy and blood) and translate the techniques derived in experimental animals to human subjects., Methods: This small review explores research conducted on the nervous system of the intestines, with an emphasis on the translation of findings from animal to human., Results: This work shows that new techniques of immunohistochemistry and retrograde tracing, developed in animal tissue, have greatly expanded our knowledge of the structure of the human enteric nervous system., Conclusions: Such findings have sparked therapeutic trials for the treatment of gastrointestinal disorders in patients., (© 2022 Royal Australasian College of Surgeons.)

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., Methods: Human colonic tissue from seven patients was fixed and dissected prior to multi-layer immunohistochemistry for human RNA binding proteins C and D (HuC/D) (pan-neuronal cell body labelling), tyrosine hydroxylase (TH, catecholaminergic labelling), Enkephalin (ENK), choline acetyltransferase (ChAT, cholinergic labelling) and/or nitric oxide synthase (NOS, nitrergic labelling) and imaged using confocal microscopy. TH-immunoreactive varicose nerve endings and myenteric cell bodies were reconstructed as three dimensional digital images. Data was exported to a purpose-built software package which quantified the density of varicosities close to the surface of each myenteric cell body., Results: TH-immunoreactive varicosities had a greater mean density within 1 μm of the surface of ChAT +/NOS- nerve cell bodies compared with ChAT-/NOS + cell bodies. Similarly, ENK-immunoreactive varicosities also had a greater mean density close to ChAT +/NOS- cell bodies compared with ChAT-/NOS + cells., Conclusion: A method for quantifying close associations between varicosities and nerve cell bodies was developed. Sympathetic axons in the myenteric plexus preferentially target cholinergic excitatory cells compared to nitrergic neurons (which are largely inhibitory). This connectivity is likely to be involved in inhibitory modulation of human colonic motility by the sympathetic nervous system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Parker, Wiklendt, Humenick, Chen, Sia, Wattchow, Dinning and Brookes.)

This chapter reviews data on the pathways by which luminal, mainly duodenal, chemoreceptors modulate gastro-pyloro-duodenal motor function to control emptying of nutrients into the small intestine. The vagus mediates proximal gastric relaxation caused by nutrient stimulation of duodenal/jejunal mucosal chemoreceptors. Modulation of the spatial patterning and inhibition of antral contractions during duodenal chemoreceptor activation are somewhat conflicting: both vagal control and ascending intramural nerves appear to play a role. Intraduodenal nutrients stimulate the localized pyloric contractions that prevent transpyloric flow via ascending duodenal intramural nerve pathways. Though not yet formally investigated, patterns of activation of the duodenal brake motor mechanism suggest that duodenal loop mucosal chemoreceptors signal to a brake mechanism at the most aborad region of the duodenum via descending intramural duodenal nerves.Intrinsic intramural pathways are important in the control of the first stages of digestion., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The colon plays an important functional role in the bacterial fermentation of carbohydrates, transmural exchange of fluid and short-chain fatty acids, and the formation, storage and evacuation of faeces and gaseous contents. Coordinated colonic motor patterns are essential for these functions to occur. Our understanding of human colonic motor patterns has largely come through the use of various forms of colonic manometry catheters, combined with a range of stimuli, both physiological and artificial. These stimuli are used in patients with colonic disorders such as constipation, irritable bowel syndrome and faecal incontinence to understand the pathophysiology mechanisms that may cause the disorder and/or the associated symptoms. However, our understanding of a "normal" colonic response remains poor. This review will assess our understanding of the normal colonic response to commonly used stimuli in short duration studies (<8 hrs) and the mechanisms that control the response., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

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. Protocol 1 (n = 10) compared pressure and impedance prior to and after a meal. Protocol 2 (n = 9) compared pressure and impedance before and after gas insufflation into the sigmoid colon (60 mL total volume)., Key Results: Both the meal and gas insufflation resulted in an increase in the prevalence of the 2-8/minute "cyclic motor pattern" (meal: (t(9) = -6.42, P<0.001); gas insufflation (t(8) = -3.13, P = 0.01)), and an increase in the number of antegrade and retrograde propagating impedance events (meal: Z = -2.80, P = 0.005; gas insufflation Z = -2.67, P = 0.008). Propagating impedance events temporally preceded antegrade and retrograde propagating contractions, representing a column of luminal gas being displaced ahead of a propagating contraction. Three participants reported an urge to pass flatus and/or flatus during the studies., Conclusions and Inferences: Initiation of the 2-8/minute cyclic motor pattern in the distal colon occurs both following a meal and/or as a localized sensorimotor response to gas. The near-absence of a flatal urge and the temporal association between propagating contractions and gas transit supports the hypothesis that the 2-8/minute cyclic motor pattern acts as a physiological "brake" modulating rectal filling., (© 2021 John Wiley & Sons Ltd.)

Background: Cyclic motor patterns (CMPs) are the most common motor pattern in the distal colon. This study used high-resolution (HR) colonic manometry to quantify trends in distal colonic motor activity before elective colonic surgery, determine the effect of a preoperative carbohydrate load, and compare this with a meal response in healthy controls., Methods: Fiber-optic HR colonic manometry (36 sensors, 1 cm intervals) was used to investigate distal colonic motor activity in 10 adult patients prior to elective colonic surgery, 6 of whom consumed a preoperative carbohydrate drink (200 kCal). Data were compared with nine healthy volunteers who underwent HR colonic manometry recordings while fasted and following a 700 kCal meal. The primary outcome was the percentage of recording occupied by CMPs, defined as propagating contractions at 2-4 cycles per minute (cpm). Secondary outcomes included amplitude, speed, and distance of propagating motor patterns., Results: The occurrence of CMPs progressively increased in time periods closer to surgery (p = 0.001). Consumption of a preoperative drink resulted in significantly increased CMP occurrence (p = 0.04) and propagating distance (p = 0.04). There were no changes in amplitude or speed of propagating motor patterns during the preoperative period. The increase in activity following a preoperative drink was of similar magnitude to the colonic meal response observed in healthy controls, despite the lesser caloric nutrient load., Conclusion: Distal colonic CMP increased in occurrence prior to surgery, amplified by ingestion of preoperative carbohydrate drinks. We hypothesize that anxiety, which is also known to rise with proximity to surgery, could play a contributing role., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: A significant proportion of children experience bowel dysfunction (including constipation and fecal incontinence) following surgical repair of Hirschsprung disease (HD). Persistent symptoms are thought to relate to underlying colonic and/or anorectal dysmotility. Manometry may be used to investigate the gastrointestinal motility patterns of this population., Purpose: To (1) evaluate the colonic manometry equipment and protocols used in the assessment of the post-operative HD population and (2) summarize the available evidence regarding colonic motility patterns in children with HD following surgical repair., Data Sources: We performed a systematic review of the Cochrane Library, Embase, MEDLINE, and PubMed databases (January 1, 1980 and March 9, 2020). Data were extracted independently by two authors., Study Selection: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting the post-operative assessment of children with HD using colonic manometry were considered for inclusion., Results: Five studies satisfied selection criteria, providing a combined total of 496 children. Of these, 184 children with repaired HD underwent colonic manometry. Studies assessed heterogeneous populations, utilized variable manometry equipment and protocols, and reported limited baseline symptom characteristics, thus restricting comparability. All studies used low-resolution colonic manometry., Conclusions: This systematic review highlighted the paucity of evidence informing the understanding of colonic dysmotility in the post-operative HD cohort. Current literature is limited by variable methodologies, heterogeneous cohorts, and the lack of high-resolution manometry., (© 2021 John Wiley & Sons Ltd.)

The act of defaecation, although a ubiquitous human experience, requires the coordinated actions of the anorectum and colon, pelvic floor musculature, and the enteric, peripheral and central nervous systems. Defaecation is best appreciated through the description of four phases, which are, temporally and physiologically, reasonably discrete. However, given the complexity of this process, it is unsurprising that disorders of defaecation are both common and problematic; almost everyone will experience constipation at some time in their life and many will develop faecal incontinence. A detailed understanding of the normal physiology of defaecation and continence is critical to inform management of disorders of defaecation. During the past decade, there have been major advances in the investigative tools used to assess colonic and anorectal function. This Review details the current understanding of defaecation and continence. This includes an overview of the relevant anatomy and physiology, a description of the four phases of defaecation, and factors influencing defaecation (demographics, stool frequency/consistency, psychobehavioural factors, posture, circadian rhythm, dietary intake and medications). A summary of the known pathophysiology of defaecation disorders including constipation, faecal incontinence and irritable bowel syndrome is also included, as well as considerations for further research in this field., (© 2021. Springer Nature Limited.)

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. We then used video imaging of colonic wall movements with electromyography in isolated preparations containing guinea-pig proximal colon, colonic flexure and distal colon. To investigate the pellet formation process, the colonic segments were infused with artificial contents (Krebs solution and 4-6% methylcellulose) to simulate physiological faecal content flow. Remarkably, pellet formation took place in vitro, without extrinsic neural inputs. Infusion evoked slowly propagating neurogenic contractions, the proximal colon migrating motor complexes (∼0.6 cpm), which initiated pellet formation at the flexure. Lesion of the flexure, but not the proximal colon, disrupted the formation of normal individual pellets. In addition, a distinct myogenic mechanism was identified, whereby slow phasic contractions (∼1.9 cpm) initiated at the flexure and propagated short distances retrogradely into the proximal colon and antegradely into the distal colon. There were no detectable changes in the density or distribution of pacemaker-type interstitial cells of Cajal across the flexure. The findings provide new insights into how solid faecal content is generated, suggesting the major mechanisms underlying faecal pellet formation involve the unique interaction at the colonic flexure between antegrade proximal colon migrating motor complexes, organized by enteric neurons, and retrograde myogenic slow phasic contractions. Additional, as yet unidentified extrinsic and/or humoral influences appear to contribute to processing of faecal content in vivo. KEY POINTS: In herbivores, including guinea-pigs, clearly defined faecal pellets are formed at a distinct location along the large intestine (colonic flexure). The mechanism underlying the formation of these faecal pellets at this region has remained unknown. We reveal a progressive and gradual reduction in water content of faecal content along the bowel. Hence, the distinct transition from amorphous to pellet shaped faecal content could not be explained by a dramatic increase in water reabsorption from a specific site. We discovered patterns of anterograde neurogenic and retrograde myogenic motor activity that facilitate the formation of faecal pellets. The formation of 'pellet-like' boluses at the colonic flexure involves interaction of an antegrade migrating motor complex in the proximal colon and retrograde myogenic slow phasic contractions that emerge from the colonic flexure. The findings uncover intrinsic mechanisms responsible for the formation of discrete faecal scybala in the large intestine of a vertebrate., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

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. Twenty-seven children (9.3 ± 1.2 yr) undergoing simultaneous high-resolution antroduodenal and colonic manometry were included. Small bowel and colonic motor patterns were assessed before and after colonic infusion of bisacodyl. Patients were divided into two groups: responders and nonresponders based on the presence of high-amplitude propagating contractions (HAPCs) after bisacodyl infusion. Nineteen patients were responders. A total of 188 postbisacodyl HAPCs was identified with a mean count of 10.4 ± 5.5 (range, 3-22), at a frequency of 0.6 ± 0.2/min and mean amplitude of 119.8 ± 23.6 mmHg. No motor patterns were induced in the small bowel. However, in the 19 responders the onset of HAPCs was associated with a significant decrease in small bowel contractile activity. In the nonresponders, there was no detectable change in small bowel motility after bisacodyl infusion. Bisacodyl-induced HAPCs are associated with a significant reduction in small bowel motility probably mediated by extrinsic sympathetic reflex pathways. This inhibition is potentially related to rectal distension, caused by the HAPC anal propulsion of colonic content. NEW & NOTEWORTHY The present study has shown, for the first time, that the presence of high-amplitude propagating contractions induced by bisacodyl is associated with a significant reduction in small bowel motility. These findings support of possible existence of a reflex pathway that causes inhibition of small bowel motility in response to rectal distension.

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)., Methods: We recorded propulsive and non-propulsive neurogenic motor activity in mouse large intestine under six different stimulus conditions of varying viscosities. Gut wall movements were recorded by video and smooth muscle electrical behavior recorded with extracellular suction electrodes., Key Results: Three major neurally mediated motor patterns contributed to pellet formation and propulsion. (1) Pellet-shaped boluses are pinched off near the ceco-colonic junction and slowly propelled distally to a transition located at 40% length along the colon. (2) At this functional colonic flexure, propulsion speed is significantly increased by self-sustaining neural peristalsis. Speed transition at this location also occurs with artificial pellets and with spontaneously formed boluses in the empty colon. (3) Periodic colonic motor complexes (CMCs) were present in all conditions reaching a maximal frequency of about 0.4 cpm and extending across the proximal and distal colon with faster speed of propagation., Conclusions and Inferences: The three motor patterns share a unique underlying fundamental property of the enteric circuits, which involve extended ensembles of enteric neurons firing at close to 2 Hz. The demonstration of distinct functional differences between proximal and distal colon in rabbit, guinea pig, and now mouse raises the possibility that this may be an organizational principle in other mammalian species, including humans., (© 2021 John Wiley & Sons Ltd.)

Background: Chronic constipation is a prevalent disorder that affects patients' quality of life and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology & Motility journal supplement devoted to the investigation and management of constipation was published (2009; 21 (Suppl.2)). This included seven articles, disseminating all themes covered during a preceding 2-day meeting held in London, entitled "Current perspectives in chronic constipation: a scientific and clinical symposium." In October 2018, the 3rd London Masterclass, entitled "Contemporary management of constipation" was held, again over 2 days. All faculty members were invited to author two new review articles, which represent a collective synthesis of talks presented and discussions held during this meeting., Purpose: This article represents the first of these reviews, addressing epidemiology, diagnosis, clinical associations, pathophysiology, and investigation. Clearly, not all aspects of the condition can be covered in adequate detail; hence, there is a focus on particular "hot topics" and themes that are of contemporary interest. The second review addresses management of chronic constipation, covering behavioral, conservative, medical, and surgical therapies., (© 2020 John Wiley & Sons Ltd.)

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. Proximal and distal segments were studied separately in organ baths with oxygenated Krebs solution, maintained at either 15°C (n = 5) or 25°C (n = 6). Motility was analyzed during rest, after oral infusion of Krebs solution, and after application of hexamethonium (100 µM) and tetrodotoxin (TTX) (0.6 µM)., Key Results: Antegrade and retrograde propagating contractions (PC) were recorded in all preparations. In the proximal intestine, at 15 and 25°C, retrograde PCs occurred at 2.7 [1.7-4.5] and 3.1 [1.6-6.5] times the frequency of antegrade PCs, respectively. Colder temperatures did not inhibit PC frequency. Hexamethonium did not inhibit PC, and however, TTX abolished all contractile activity., Conclusions and Inferences: Both neurogenic antegrade and retrograde propagating contractions occur throughout the intestine of Silver Perch. However, unlike the mammalian colon, these motor patterns do not require enteric nicotinic transmission and they are not inhibited by cold temperatures (15°C). Therefore, while the GI motility patterns in Silver Perch resemble those recorded from the colon of mammals, there may be differences in the mechanisms that underlying their generation., (© 2020 John Wiley & Sons Ltd.)

Background: Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder., Purpose: This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition., (© 2020 John Wiley & Sons Ltd.)

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. In addition, electrical activity of smooth muscle was recorded by suction electrodes., Key Results: Two distinct types of CMCs were distinguished; CMCs that propagated along the entire colon (complete CMC) and CMCs which were restricted to the proximal colon (incomplete CMC). The two types of CMC often occurred in the same preparations. Incomplete CMCs had longer bursts of smooth muscle action potentials than complete CMCs and propagated more slowly. Interestingly, both types of CMC were associated with similar frequency bursts of smooth muscle action potentials at ~2.4 Hz. In the most proximal colon, an additional firing frequency was detected close to ~7 Hz generating multiple peaks within each CMC., Conclusions & Inferences: We report distinct characteristics underlying complete and incomplete CMCs in isolated mouse colon. Recognizing these distinct patterns of motility will be important for future interpretation of analysis of murine colonic motility recordings. The identification of alternating patterns of motor activity in proximal colon, but not distal colon may reflect specific neural mechanisms for fecal pellet formation., (© 2020 John Wiley & Sons Ltd.)

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. Statistical inference is achieved by modeling the resulting time-averaged amplitudes in the frequency and frequency-phase domains as Gaussian processes over a regular grid, under the influence of categorical and numerical predictors specified by the experimental design as a functional mixed-effects model. Parameters of the model are inferred with Hamiltonian Monte Carlo. Using this method, we re-analyzed our previously published colonic manometry data, comparing healthy controls and patients with slow transit constipation. The output from our automated method, supports and adds to our previous manual analysis. To obtain these results took less than two days. In comparison the manual analysis took 5 weeks. The proposed mixed-effects model approach described here can also be used to gain an appreciation of cyclical activity in individual subjects during control periods and in response to any form of intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wiklendt, Costa, Scott, Brookes and Dinning.)

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., Results: Qualitatively (by visual inspection of HR-ARM recordings), the frequency of slow-wave pressure activity was strikingly different in 11/21 (52.4%) LARS patients from that observed in all the healthy individuals. Quantitative analysis showed that peaks of the mean spectrum in these 11 LARS patients occurred at approximately 6-7 cycles per minute (cpm), without activity at higher frequencies. An equivalent pattern was found in only 2/37 (5.4%) healthy individuals (P < 0.0001). Peaks of the mean spectrum in healthy individuals were concentrated at 16 cpm and 3-4 cpm., Conclusion: Over half of the male LARS patients studied had altered anal slow-wave pressure activity based on analysis of HR-ARM recordings. Further studies could investigate the relative contributions of sex, human baseline variance and neoadjuvant/surgical therapies on anal slow waves, and correlate the presence of abnormal activity with symptom severity., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Rationale: Colonic high-resolution manometry (cHRM) is an emerging clinical tool for defining colonic function in health and disease. Current analysis methods are conducted manually, thus being inefficient and open to interpretation bias., Objective: The main objective of the study was to build an automated system to identify propagating contractions and compare the performance to manual marking analysis., Methods: cHRM recordings were performed on 5 healthy subjects, 3 subjects with diarrhea-predominant irritable bowel syndrome, and 3 subjects with slow transit constipation. Two experts manually identified propagating contractions, from five randomly selected 10-min segments from each of the 11 subjects (72 channels per dataset, total duration 550 min). An automated signal processing and detection platform was developed to compare its effectiveness to manually identified propagating contractions. In the algorithm, individual pressure events over a threshold were identified and were then grouped into a propagating contraction. The detection platform allowed user-selectable thresholds, and a range of pressure thresholds was evaluated (2 to 20 mmHg)., Key Results: The automated system was found to be reliable and accurate for analyzing cHRM with a threshold of 15 mmHg, resulting in a positive predictive value of 75%. For 5-h cHRM recordings, the automated method takes 22 ± 2 s for analysis, while manual identification would take many hours., Conclusions: An automated framework was developed to filter, detect, quantify, and visualize propagating contractions in cHRM recordings in an efficient manner that is reliable and consistent.