Results of 24-h manometric recording of colonic motor activity with endoluminal instillation of bisacodyl in patients with severe chronic slow transit constipation

The aims of this study were to assess the prevalence of manometric colonic abnormalities and to evaluate the motor effect of intraluminal bisacodyl in a cohort of refractory constipated patients. Twenty-four hour colonic motility recordings were performed in 40 patients referred for a severe intractable chronic constipation. At the end of each recording session the motor effects of the endoluminal instillation of 10 mg bisacodyl were assessed. These patients were compared with 20 healthy subjects. The number of high-amplitude propagating contractions (HAPC) was significantly decreased in patients with slow transit constipation (12 +/- 11.6 vs 1 +/- 8.6, P < 0.001). Based on manometric patterns four groups of patients were isolated. Ten patients had no spontaneous HAPC, no food-induced colonic motor response and significantly lower colonic activity in transverse colon (374 +/- 1220 vs 3249 +/- 3458, P < 0.05). Five patients had significantly increased sigmoid segmental motility (20298 +/- 6364 vs 88780 +/- 3643, P < 0.001) and eight patients had significantly lower number of HAPC without other manometric abnormalities while 17 patients had normal colonic motility recordings. Endoluminal bisacodyl was able to induce HAPCs in all groups of patients. Patients with severe slow transit refractory constipation represented a heterogeneous group and endoluminal bisacodyl was able to promote a propagated motor activity in a majority of patients even in those suspected of having an inert colon.     

Difficulty in estimating localized bowel contraction by colonic manometry: a simultaneous recording of intraluminal pressure and luminal calibre

To examine whether or not intraluminal pressure changes at a site in the human colon reflect with fidelity the local bowel wall contractions or relaxation, endoscopic recording of the changes in colonic calibre as a parameter of the motor events with simultaneous manometry was performed at a fixed site in a prepared sigmoid colon during the interdigestive state. In four of the 12 subjects, a total of 20 phasic pressure waves with an amplitude of 13–22 mmHg and a duration of 13–18 sec were obtained in a 20 min recording session. Eighteen of the 20 phasic pressure waves (90%) were associated not with a decrease (contraction) but with an increase in the calibre (relaxation). The pressure change began 0.2–8.4 sec (mean: 4.5 sec) behind and ended ? 1.8 to 8 sec (mean: 3.5 sec) ahead of the calibre change. In the other eight subjects, no phasic pressure change was recorded in the presence of an overt calibre change. We conclude that manometric phasic pressure change recorded at a site in the empty human colon is not necessarily correlated with the localized contractile activity. Extrapolation of pressure profiles in the colon to motor events at the manometric site should be cautious.     

Low-dose lactulose produces a tonic contraction in the human colon

Lactulose (10-20 g day(-1)) is used to treat constipation. At this therapeutic dose, its effects on colonic motility remain unknown. Twenty-two healthy subjects swallowed a probe with an infusion catheter, six perfused catheters and a balloon connected to a barostat. Colonic phasic and tonic motor activity was recorded in fasting state. In group 1, four volunteers ingested 15 g lactulose and motility was recorded for 5 h after entry of lactulose into the caecum; in group 2, motility was recorded during (3 h) and 2 h after intracolonic infusion of isoosmotic and isovolumetric solutions containing sodium chloride alone (n = 9) or with 15 g lactulose (n = 9). In a last group of volunteers, isotopic colonic transit after ingestion of lactulose (10 g,n = 9) was assessed and compared with a control group (n = 17). Ingestion or intracolonic infusion of 15 g lactulose significantly decreased barostat bag volume (maximal decrease: 45 +/- 12% and 35 +/- 9% of basal value respectively). Phasic contractions remained unchanged. Tonic and phasic motility was unchanged by the isotonic and isovolumetric infusion of saline. Ingestion of lactulose significantly accelerated isotopic colonic transit time compared with the control group. We conclude that in healthy humans, 10-15 g ingestion or intracaecal infusion of lactulose produces a prolonged tonic contraction that may be involved in the laxative effect of lactulose.     

American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice

Abstract Tests of gastric, small intestinal and colonic motor function provide relevant physiological information and are useful for diagnosing and guiding the management of dysmotilities. Intraluminal pressure measurements may include concurrent measurements of transit or intraluminal pH. A consensus statement was developed and based on reports in the literature, experience of the authors, and discussions conducted under the auspices of the American Neurogastroenterology and Motility Society in 2008. The article reviews the indications, methods, performance characteristics, and clinical utility of intraluminal measurements of pressure activity and tone in the stomach, small bowel and colon in humans. Gastric and small bowel motor function can be measured by intraluminal manometry, which may identify patterns suggestive of myopathy, neuropathy, or obstruction. Manometry may be most helpful when it is normal. Combined wireless pressure and pH capsules provide information on the amplitude of contractions as they traverse the stomach and small intestine. In the colon, manometry assesses colonic phasic pressure activity while a barostat assesses tone, compliance, and phasic pressure activity. The utility of colonic pressure measurements by a single sensor in wireless pressure/pH capsules is not established. In children with intractable constipation, colonic phasic pressure measurements can identify patterns suggestive of neuropathy and predict success of antegrade enemas via cecostomy. In adults, these assessments may be used to document severe motor dysfunction (colonic inertia) prior to colectomy. Thus, intraluminal pressure measurements may contribute to the management of patients with disorders of gastrointestinal and colonic motility.     

Comparison of simultaneous recordings of human colonic contractions by manometry and a barostat

Abstract Our hypothesis was that manometry in the colon was less sensitive than the electronic barostat in detection of colonic contractions. In ten healthy volunteers, we have characterised the pressure activity and tone of the colon by means of combined multilumen manometry and a barostatic balloon that was infinitely compliant, conformed to the colon's inner wall, and was clamped at a constant 'operating' pressure throughout the study. A computer program separated indices of the colon's motor function detected by the barostat: a baseline volume and phasic volume events. The barostat detects on average 70% more phasic pressure events than manometric sideholes located 2 em proximal to 7 cm distal to the balloon. Manometry becomes less sensitive than the barostat when the colonic diameter exceeds 5.6 em. The barostat detects on average 90% of all propagated and non-propagated (>30 mmHg) manometric peaks. The baseline volume changes significantly after the ingestion of a 1000-kcal meal, consistent with an increment in colonic tone, undetected by manometry. A combined barostat—manometry assembly appears to be preferable to manometry alone in the intraluminal evaluation of human colonic pressure activity and tone.     

Effect of motilin and erythromycin on the motor activity of the human colon

Motilin and motilin receptor agonist erythromycin were administered to healthy subjects where colonic motility was recorded manometrically from the hepatic flexure to the rectum. Experiments were carried out during the fasting basal state or when colonic motility was stimulated by the ingestion of a 1000 kcal lunch. A supraphysiological dose of motilin (100 ng kg^?1, i.v.) increased the motor activity of the fasting sigmoid colon, but the response was smaller than the meal induced activity. The administration of erythromycin (200 mg, i.v.) during the inter digestive period induced, on the sigmoid region, a motor response that was not significantly different in amplitude from the post-prandial contractile profile. However, on the more proximal segments of the colon, motilin and erythromycin were inactive. When both agents were administered during the digestive period, both failed to modify the contractile stimulation normally seen in all regions of the colon after a meal. Therefore the colonic motor response obtained with stimulation of motilin receptors in man appears limited;it is restricted to the sigmoid, it can be seen only during fasting and it is of weak amplitude.     

Altered periodic rectal motor activity: a mechanism for slow transit constipation

The pathophysiology of slow transit constipation is poorly understood. Both decreased and increased distal colonic motility have been reported. In healthy humans, a 3 cycles per minute (cpm), periodic rectal motor activity (PRMA) has been described. Our aim was to investigate the characteristics of PRMA and to assess its role in the pathogenesis of constipation. A six-sensor solid-state probe was placed with the tip sensor in the mid-transverse colon, without sedation, and prolonged colonic motility was recorded in nine patients with slow transit constipation (1M, 8F) and in 11 healthy subjects (3M, 8F). Subjects were free to ambulate. We examined the frequency, nocturnal vs. diurnal variation, and characteristics of PRMA, and its relationship to proximal colonic motility. All subjects showed PRMA. The rhythm was similar (2.5-4 cpm) in both groups. However, constipated patients exhibited a greater (P < 0.001) number of PRMA cycles than controls. The duration of each cycle and amplitude of pressure waves during PRMA were also greater (P < 0.05) at night in patients compared with controls. In patients, 40% of PRMA cycles were associated with a proximal colonic motor event compared with 81% in controls (P < 0.02). The area under the curve of all colonic pressure waves and incidence of specialized propagating pressure waves was lower (P < 0.05) in patients during daytime. When compared with controls, constipated patients exhibited reduced daytime colonic pressure waves and a higher frequency of PRMA. Most of the PRMA was unrelated to proximal colonic activity in constipated patients in contrast with findings in control patients. In addition to decreased colonic motility, this excessive and unco-ordinated phasic rectal activity may further impede stool transport and contribute to the pathogenesis of slow transit constipation.     

Recto-colonic reflex is impaired in patients with irritable bowel syndrome

Motor and sensory dysfunction of the gut are present in a subset of patients with irritable bowel syndrome (IBS). Recent studies have demonstrated the presence of a recto-colonic inhibitory reflex in healthy humans. It is not known whether this reflex exists in IBS. We studied rectal compliance, perception and the recto-colonic reflex by measuring volume responses of the descending colon to rectal distentions by barostat in 26 IBS patients and 13 healthy controls under both fasting and postprandial conditions. In the fasting state, rectal distention inhibited colonic tone and phasic motility to a similar extent in health and IBS. After a meal, rectal distention inhibited colonic tone and phasic motility to a lesser degree (P < 0.05) in IBS than health. Under postprandial but not fasting conditions, rectal distentions of increasing intensity were associated with higher pain scores in IBS than in health. Rectal distention inhibits tonic and phasic motility of the descending colon in healthy controls and in IBS patients. Postprandially this recto-colonic inhibitory reflex is impaired and attenuated in IBS patients compared with controls. These findings point to an altered reflex function in IBS and have implications for pathophysiology and therapy.     

Fermentation of starch stimulates propagated contractions in the human colon

Background In healthy humans, up to 30 g of daily ingested starch escape small intestinal digestion, and are fermented in the colon. This physiological starch malabsorption could modify colonic motility through metabolites such as short‐chain fatty acids produced by fermentation. Methods Ten healthy volunteers swallowed a probe, consisting of an infusion catheter, six perfused catheters and a balloon connected to a barostat. On two consecutive days colonic motility was recorded in fasting subjects in the basal state (1 h), and then during (3 h), and after (2 h) the intracolonic infusion of 750 mL of isoosmotic and isovolumetric solutions containing sodium chloride with or without 15 g wheat starch. We determined (i) the volume of hydrogen and methane exhaled in breath, (ii) a global motility index and the number of high amplitude propagated contractions (HAPCs), and (iii) the mean balloon volume, reflecting the tonic motor activity. Key Results [median (IQR)] Compared to the basal period, colonic infusion of starch or saline did not modify the colonic motility index and tone. However, the number of HAPCs was significantly higher during and after infusion of starch than of saline [4.5 (2.75–6.5) vs 0.96 (0–2.66)/5 h, starch vs saline respectively; P = 0.011]. Conclusions & Inferences In healthy humans, colonic fermentation of a physiological malabsorbed amount of starch has no effect on the tonic and phasic colonic motor activities, but produces a significant increase in the number of HAPCs. This may participate in the physiological propulsion of colonic contents.     

Characterization of colonic motor activity in conscious dogs

Diurnal changes in canine colonic motility were investigated by means of chronically implanted force transducers. A characteristic of the colonic motor profile in the fasted state was the occurrence of colonic motor complexes consisting of tonic contractions superimposed with phasic ones. On feeding, motor complexes were immediately induced in the whole colon and continued to occur at significantly shorter intervals than those in the fasted state, but the duration and the amplitude of the colonic motor complexes were not affected by feeding. This increased activity period lasted for 8–16 h after feeding, and 83.3% of the defecations were observed in this period. Of the defecations 33% occurred in the first 2 h after feeding (P < 0.05). More than 80% of the giant migrating contractions associated with defecation propagated from the middle to the distal colon, and the start of faeces evacuation coincided with the end of the relaxation period of the distal colon preceding the arrival of the giant migrating contractions. More than 90% of the giant migrating contractions not associated with defecation migrated from the proximal to the middle colon. More than 60% of the colonic motor complexes migrated in an aboral direction and about 18% of them in an oral direction. These results suggest that (1) defecations tend to occur immediately after feeding; (2) the regional distribution of giant migrating contractions was different between those associated and not associated with defecation.     

Anatomical registration and three‐dimensional visualization of low and high‐resolution pan‐colonic manometry recordings

Background Colonic propagating sequences (PS) are important for the movement of colonic content and defecation, and aberrant PS patterning has been associated with slow transit constipation. However, because these motor patterns are typically recorded over long periods (24 h +), the visualization of PS spatiotemporal patterning is difficult. Here, we develop a novel method for displaying pan‐colonic motility patterns. Methods A 3D mesh representing the geometry of the human colon was created as follows: (i) Human colon images from the Visible Human Dataset were digitized to create a 3D data cloud, and (ii) A surface mesh was fitted to the cloud using a least‐squares minimization technique. Colonic manometry catheters were placed in the ascending colon of healthy controls and patients with slow transit constipation (STC), with the aid of a colonoscope. The colonic manometry data were interpolated and mapped to the model according to the following anatomical landmarks: cecum, hepatic flexure, splenic flexure, sigmoid‐descending junction, and anus. Key Results These 3D images clearly and intuitively communicate characteristics of normal and abnormal colonic motility. Specifically we have shown the reduced amplitude of the antegrade propagating pressure waves (PPW) throughout the colon and reduced frequency of PPWs at the mid‐colon in patients with STC. Conclusions and Inferences A novel method for the 3D visualization of PS is presented, providing an intuitive method for representing a large volume of physiological data. These techniques can be used to display frequency, amplitude or velocity data, and will help to convey regions of abnormally in patient populations.     

Pancolonic spatiotemporal mapping reveals regional deficiencies in,and disorganization of colonic propagating pressure waves in severe constipation

Background The morphology, motor responses and spatiotemporal organization among colonic propagating sequences (PS) have never been defined throughout the entire colon of patients with slow transit constipation (STC). Utilizing the technique of spatiotemporal mapping, we aimed to demonstrate ‘manometric signatures’ that may serve as biomarkers of the disorder. Methods In 14 female patients with scintigraphically confirmed STC, and eight healthy female controls, a silicone catheter with 16 recording sites spanning the colon at 7.5 cm intervals was positioned colonoscopically with the tip clipped to the cecum. Intraluminal pressures were recorded for 24 h. Key Results Pan‐colonic, 24 h, spatiotemporal mapping identified for the first time in STC patients: a marked paucity of propagating pressure waves in the mid‐colon (P = 0.01), as a consequence of a significant (P < 0.0001) decrease in extent of propagation of PS originating in the proximal colon; an increase in frequency of retrograde PS in the proximal colon; a significant reduction in the spatiotemporal organization among PS (P < 0.001); absence of the normal nocturnal suppression of PS. Conclusions & Inferences Pan‐colonic, 24 h, spatiotemporal pressure mapping readily identifies characteristic disorganization among consecutive PS, regions of diminished activity and absent or deficient fundamental motor patterns and responses to physiological stimuli. These features are all likely to be important in the pathophysiology of slow transit constipation.     

Periodic colonic motor activity identified by 24-h pancolonic ambulatory manometry in humans

The pattern of colonic motor activity in healthy humans has not been fully elucidated to date. The aim of this study was to evaluate colorectal motor activity employing 24-h ambulant pancolonic manometry. Ten healthy volunteers (6F, 4M), aged 19-31 years were studied. Motor activity was measured using two custom-made silicone coated catheters, each with five solid-state pressure transducers. No bowel preparation or sedation was used. The study period was 24 h. A total of 232 h of recording was obtained. Sixty-three high amplitude propagated contractions were observed, median six per 24-h period. Low-amplitude colonic contractile activity showed regional and diurnal variations. Frequency of contraction was highest in the right colon [median 5.26 cpm (cycles per minute)], and transverse colon and splenic flexure (median 5.15 cpm). The interval between colonic motor complexes was shortest in the transverse colon and splenic flexure. This study introduces a new technique for the evaluation of colorectal motor activity. Subjects were studied in an ambulant setting in their own environment ensuring that this method of study is as physiological as possible. This study demonstrates that colonic motor activity has two main components: high amplitude propagated contractions and low amplitude colonic contractile activity.     

Wood creosote prevents CRF-induced motility via 5-HT3 receptors in proximal and 5-HT4 receptors in distal colon in rats

Wood creosote has been used as an herbal medicine against acute diarrhea caused by food poisoning and has an inhibitory effect on colonic motility and enterotoxin-induced ion secretion. Since no previous studies have examined the effects of wood creosote on stress-induced alteration of colonic motility, we examined the effects on the colonic motility altered by intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF), which is a key mediator in responses to stress. We recorded motor activity in proximal and distal colon of unrestrained conscious rats via two manometory catheters. The frequencies of phase III-like contraction and the % motor indices in both proximal and distal colon were measured. At the same time the number of fecal pellets excreted was counted. I.c.v. injection of CRF increased the motor activity in both proximal and distal colon, and these effects were completely antagonized by i.c.v. injection of a selective CRF type 1 antagonist but not by a CRF type 2 antagonist. Changes in colonic motility induced by CRF were reversed by intravenously administered wood creosote. Intraluminal administration of the 5-HT(3) receptor antagonist granisetron, or the 5-HT(4) receptor antagonist SB 204070 blocked the increase in colonic motility induced by i.c.v. injection of CRF. Wood creosote prevented the increase in colonic motility induced by the 5-HT(3) receptor agonist SR57227A in the proximal colon, while it prevented the increase in colonic motility induced by the 5-HT(4) receptor agonist RS67506 in the distal colon. These results indicate that wood creosote prevents the increase in colonic motility induced by CRF via 5-HT(3) receptors in the proximal colon, and via 5-HT(4) receptors in the distal colon, suggesting that wood creosote might be useful to treat stress-induced diarrhea.     

Validation of a semi-automated scintigraphic technique for detecting episodic, real-time colonic flow

The relationships between the movement of colonic content and regional pressures have only been partially defined. During the analysis of a combined colonic scintigraphic and manometric study, a quantitative technique for determining discrete, episodic, real-time colonic flow was developed. Our aim was to validate this technique through the construction of a computer-generated phantom model of known antegrade and retrograde motility. The anthropoid phantom was rasterized into a 6-mm voxel model to create a 3D voxel phantom of the colon with four distinct colonic segments. Associating a time/activity curve with each segment simulated dynamic behaviour. Activity in the model was based on data obtained from human colonic scintigraphic recordings using 30 MBq of (99m)Tc sulphur colloid. The flow was simulated by modifying the input time/activity functions to represent episodes of net flow of 2%, 5% or 10% of segmental content. Our quantitative technique was applied to the phantom model to measure the accuracy with which simulated flows were detected. Our quantitative technique proved to be a sensitive and specific means of detecting the presence and the magnitude of discrete episodes of colonic flow and therefore, should improve our ability to correlate colonic flow and motor patterns.     

Neural and non-neural mediation of propionate-induced contractile responses in the rat distal colon

Short-chain fatty acids (SCFAs), including propionate, butyrate and acetate, are fermentation products of carbohydrates in the colon. We investigated the contractile effects of SCFAs on the rat distal colon. Mechanical activity of the circular muscle in strip preparations was recorded in vitro. Propionate and butyrate concentration-dependently (10 micromol L(-1)-10 mmol L(-1)) induced rapid, large amplitude phasic contractions (the first phase) followed by tonic contractions (the second phase). Acetate itself had no effect on muscle activity, although preincubation with acetate attenuated both phases of the propionate-induced response. The propionate-induced phasic contraction was attenuated by atropine, tetrodotoxin and the 5-HT4 receptor antagonist SB-204070. The propionate-induced tonic contraction was attenuated by the cyclo-oxygenase inhibitor piroxicam. Antagonists of 5-HT1A, 5-HT2A and 5-HT3 receptors had no effect on the responses. Propionate-induced responses were not observed in mucosa-free preparations. These results suggest that propionate acts on receptors in the mucosa causing the release of 5-HT from enterochromaffin cells. 5-HT acts through 5-HT4 receptors on the endings of intrinsic primary afferent neurones that in turn activate cholinergic motor neurones that contract the circular muscle. Propionate also causes tonic contraction, via prostaglandin release, in the rat distal colon.     

TRH stimulation and L-glutamic acid inhibition of proximal gastric motor activity in the rat dorsal vagal complex

The importance of the dorsal vagal complex (DVC) in the control of gastric motor activity has been previously established by electrical and chemical stimulation of this region. We have further evaluated excitatory and inhibitory influences on motor activity of the gastric corpus by microinjection of L-glutamic acid (GLU) and thyrotropin-releasing hormone (TRH) into the DVC. GLU and TRH were ejected by pressure (20-30 psi) in 1-10 nl vol. from multibarreled micropipettes and intraluminal pressure in the gastric corpus was measured using a manometric catheter placed into the stomach through the pylorus of urethane-chloralose anesthetized rats. Gastric motor activity was monitored while micropipettes were advanced from the surface of the dorsomedial medulla to a depth of 1 mm in 100 micron increments. Microinjections of GLU (1-10 pmol) at depths of 200-600 microns below the surface of the brainstem caused a decrease in tonic intraluminal pressure and amplitude of phasic contractions of the gastric corpus. Injection of TRH (1-10 pmol) at depths of 200-800 microns increased both tonic intraluminal pressure and amplitude of phasic contractions. The responses to GLU (10 pmol) and TRH (10 pmol) were abolished by hexamethonium and vagotomy; atropine abolished the effect of TRH and attenuated that of GLU. It is concluded that GLU evokes only vagally mediated inhibitory effects on tonic and phasic gastric motor activity when microinjected into the DVC. In contrast, injection of TRH at the same loci causes only vagal cholinergic increases in motor activity. Subpopulations of neurons in the DVC may, therefore, be activated by specific neurotransmitters having opposite effects on gastric motor activity.     

The contribution of protein kinase C and CPI-17 signaling pathways to hypercontractility in murine experimental colitis

Background Colonic smooth muscle contractility is altered in colitis, and several protein kinase pathways can mediate colonic smooth muscle contraction. In the present study, we investigated whether protein kinase C (PKC) pathways also play a role in colonic hypercontractility observed during T_H2 colitis in BALB/c mice. Methods Colitis was induced in BALB/c mice by provision of 5% dextran sodium sulfate (DSS) for 7 days. Changes in smooth muscle contractility were examined using dissected circular smooth muscle preparations from the distal colon. The contribution of conventional and novel PKC isozymes to the hypercontractile response was examined with pharmacological PKC inhibitors. Western blot analyses were used to examine protein expression and phosphorylation changes. Key Results Colonic smooth muscle was associated with inflammation‐induced hypercontractility and altered PKC expression. Carbachol‐induced peak (phasic) and sustained (tonic) contractions were increased. Chelerythrine was the most effective PKC inhibitor of both phasic and tonic contractions. There was no general difference in the percent contribution of conventional and novel PKC isozymes toward the DSS‐induced hypercontractility, but inhibition of sustained force with GF109203x was higher for inflamed muscle. The CPI‐17 phosphorylation was equally suppressed in both normal and DSS conditions by Gö6976 and chelerythrine, but only for the phasic component of contraction. Conclusions & Inferences The outcomes suggest that both conventional and novel PKC isozymes contribute to the phasic and tonic contractile components of BALB/c colonic circular smooth muscle under normal conditions, with novel PKC isozymes having a greater contribution to the tonic contraction. However, no effect of inflammation was observed on the relative contribution of PKC and CPI‐17 toward the observed hypercontractility.     

High amplitude propagated contractions

While most colonic motor activity is segmental and non‐propulsive, colonic high amplitude propagated contractions (HAPC) can transfer colonic contents over long distances and often precede defecation. High amplitude propagated contractions occur spontaneously, in response to pharmacological agents or colonic distention. A subset of patients with slow transit constipation have fewer HAPC. In this issue of Neurogastroenterology and Motility, Rodriguez et al. report that anal relaxation during spontaneous and bisacodyl‐induced HAPC exceeds anal relaxation during rectal distention in constipated children undergoing colonic manometry. Moreover, and consistent with a neural mechanism, anal relaxation often precedes arrival of HAPC in the left colon. High amplitude propagated contractions are also used to evaluate the motor response to a meal and pharmacological stimuli (e.g., bisacodyl, neostigmine) and to identify colonic inertia during colonic motility testing in chronic constipation. This editorial comprehensively reviews the characteristics, physiology and pharmacology of HAPC, their assessment by manometry, and relevance to constipation and diarrhea.     

Does co‐administration of a non‐selective opiate antagonist enhance acceleration of transit by a 5‐HT4 agonist in constipation‐predominant irritable bowel syndrome? A randomized controlled trial

Opioid neurons exhibit tonic restraint on intestinal motility; opioid antagonists stimulate peristalsis and increase transit. In vitro, 5-hydroxytryptamine (5-HT4) agonists combined with selective opioid antagonists significantly increased colonic propulsion relative to a 5-HT4 agonist alone. We hypothesized that the combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit more than either treatment alone in female constipation-predominant irritable bowel syndrome (C-IBS) patients. Our aim was to examine the effect of tegaserod 6 mg b.i.d. alone and combined with naltrexone 50 mg on intestinal transit and stool characteristics in females with C-IBS. Forty-eight patients were randomized to tegaserod alone, naltrexone alone or in combination with tegaserod or placebo for 6 days. Small bowel, ascending colon half-life (in pharmacokinetics) (t1/2), and colonic geometric centre (8, 24, 48 h) were assessed by scintigraphy. Tegaserod increased small bowel (P < 0.01) and colon transit (P < 0.01). Naltrexone did not accelerate colonic transit relative to placebo. Combination treatment did not significantly accelerate transit relative to tegaserod alone. Tegaserod and tegaserod with naltrexone resulted in looser stool form (P < 0.01). In female C-IBS patients, tegaserod accelerates small bowel and colon transit and contributed to looser stool consistency. Use of naltrexone, 50 mg, does not support the hypothesis that combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit.