Distal Colonic Motility Research Articles

A Model of Neural Cross-Talk and Irritation in the Pelvis: Implications for the Overlap of Chronic Pelvic Pain Disorders

Irritable bowel syndrome, interstitial cystitis, and other chronic pelvic pain (CPP) disorders often occur concomitantly. Neural cross-talk may play a role in the overlap of CPP disorders via the convergence of pelvic afferents. We investigated the hypothesis that afferent irritation of one pelvic organ may adversely influence and sensitize another via neural interactions. We measured pelvic organ smooth muscle and striated muscle reflexes during micturition and colorectal distention (CRD) in urethane-anesthetized rats. The effects of acute cystitis on distal colonic sensory thresholds to CRD and the effects of acute colonic irritation on micturition parameters were assessed. External urethral sphincter (EUS) electromyography (EMG) was typical for the rat, with phasic firing during micturition. External anal sphincter EMG also showed phasic firing during micturition in synchrony with EUS activity but, in addition, showed both tonic bursts and phasic firing independent of EUS activity. Before bladder irritation, graded CRDs to 40 cm H2O produced no notable changes in abdominal wall EMG activity. Following acute bladder irritation, dramatic increases in abdominal wall EMG activity in response to CRD were observed at much lower distention pressures, indicating colonic afferent sensitization. Analogously, following acute colonic irritation, bladder contraction frequency increased 66%, suggesting sensitization of lower urinary tract afferents. We report compelling evidence of bidirectional cross-sensitization of the colon and lower urinary tract in a novel experimental model. This cross-sensitization may account for the substantial overlap of CPP disorders; however, further studies are needed to fully characterize these pathways.

Nitrergic-purinergic interactions in rat distal colon motility.

Responses of rat distal colon circular muscle strips to exogenous nitric oxide (NO) and adenosine 5'-triphosphate (ATP) and to electrical field stimulation (EFS) were assessed in the absence/presence of various agents that interfere with nitrergic-purinergic pathways. Exogenous NO (10-6 to 10-4 mol L-1) elicited concentration-dependent, tetrodotoxin (TTX)-insensitive relaxations. The soluble guanylyl-cyclase (sGC) inhibitor 1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced duration and amplitude; the small conductance Ca2+-sensitive K+ (SK)-channel blocker apamin (APA) only shortened the relaxations. ODQ + APA showed a marked inhibitory effect on duration and amplitude. TTX, APA, the NO-synthase inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) and the purinergic receptor P2Y antagonist Reactive Blue 2 (RB2) shortened the relaxations by exogenous ATP (10-3 mol L-1) but did not influence the amplitude. ODQ had no effect. TTX + l-NAME did not yield a more pronounced inhibitory effect than TTX alone. The effect of ATP-gamma-S was similar to that of ATP. Electrical field stimulation (EFS) (40 V, 0.05 ms, 0.5-4 Hz for 30 s) yielded TTX-sensitive relaxations that were not altered by l-NAME, ODQ or RB2. APA shortened the relaxations. l-NAME + APA nearly abolished these relaxations. ODQ + APA and RB2 +l-NAME reduced the duration. These results suggest that distinct sets of small conductance SK-channels are involved in the amplitude and the duration of the relaxations and that NO increases their sensitivity to NO and ATP via guanosine 3',5'-cyclic monophosphate (cGMP). ATP elicits relaxations via P2Y receptors with subsequent activation of SK-channels and induces neuronal release of NO. Both nitrergic and purinergic pathways must be blocked to inhibit EFS-induced relaxations.

Distal colonic motor activity in four subgroups of patients with irritable bowel syndrome.

With the aim of improving end organ treatment, we describe a new system of classifying irritable bowel syndrome (IBS) according to clinical features into four groups, spastic colon syndrome (SCS), functional diarrhea (FD), diarrhea-predominant spastic colon syndrome (DPSCS), and midgut dysmotility (MGD). The aim of the study was to investigate fasting and postprandial distal colonic motility in the four groups of patients and to compare the results with normal controls. Distal colonic motility studies were performed in the unprepared colon. 2.5-hr recordings were made from four channels with a standard meal administered at 0.5 hr. The intubated colon was treated as a study segment and data analyzed for study segment activity index (SSAI) and number and mean amplitude of pressure peaks over 30-min epochs. Patients with SCS had significantly higher (P < 0.05) mean amplitude of pressure peaks (60 min, 120 min) and SSAI (120 min) than controls and patients with FD, DPSCS, and MGD. In contrast, patients with FD and DPSCS had significantly (P < 0.05) lower postprandial SSAI than controls and patients with SCS (60 min, 120 min). With the exception of raised postprandial mean amplitude of pressure peaks (120 min), MGD patients had normal distal colonic motility. Division of IBS patients into subgroups has highlighted significant differences in distal colonic motility that provide insights into etiopathogenesis and should assist targeting of current and newly developed therapies, particularly receptor active agents.

Twenty-four hour recordings of colonic motility in patients with diverticular disease: evidence for abnormal motility and propulsive activity.

Diverticular disease of the colon is one of the most common pathologic entities in western countries. Although altered motility of the large bowel is commonly believed to be one of the major pathophysiologic mechanisms, no convincing evidence has been reported yet. In fact, only a few conflicting studies concerning distal colonic motility (with no information on forceful propulsive activity) are available in the literature. The purpose of the present study was to investigate basal and stimulated (postprandial) colonic motility from the transverse (not affected), descending, and sigmoid colon in patients with diverticular disease, together with detection of high-amplitude propagated contractions (mass movements). Motility data from patients were compared with those obtained in healthy control subjects. Ten patients and 16 control subjects of both sexes were recruited for the study. In all subjects, colonic motility was recorded for a 24-hour period by a colonoscopically positioned manometric catheter. Two 1000-kcal mixed meals were served during the study. Compared with control subjects, patients with diverticular disease displayed significantly increased amounts of motility in the affected segments; the response to a physiologic stimulus (meal) was also abnormal in the patients' group. Diverticular disease patients also had a significant increase of forceful propulsive activity compared with control subjects (average = 10.3 +/- 2.7/subject/day high-amplitude propagated contractions for patients and 5.5 +/- 0.8/subject/day for control subjects; P = 0.051); interestingly, about 20 percent of such activity was abnormal, being propagated in a retrograde fashion. We concluded that patients with diverticular disease of the colon have abnormal motor and propulsive activities of the large bowel, which are confined to the affected segments.

Functional role of inducible nitric oxide synthase on mouse colonic motility

A possible functional role of inducible isoform of nitric oxide synthase (iNOS) was explored in vitro on the motility of mouse distal colon. Using an isotonic – non-isovolumic technique, peristaltic activity and video images of the external wall of colonic segments were recorded before and after addition to the medium of Aminoguanidine (AG) and N-(3-(aminomethyl)benzyl) acetamidine (W1400) [10 −7 M–10 −4 M], two iNOS inhibitors. AG and W1400 induced an hyperexcitability of visceral smooth muscle characterised by an increase of basal tone and spontaneous phasic activity. As a consequence of these effects, the peristaltic activity declined and disappeared at the highest concentrations. These findings indicated a removal of inhibitory action performed by NO synthesised by iNOS in the colonic segment. The implications of results are discussed in term of tonic relaxation of intestinal smooth muscle to allow intraluminal content accommodation.

The effect of a polymeric enteral formula supplemented with a mixture of six fibres on normal human bowel function and colonic motility

Background and aims: Fibres with varying fermentability may improve bowel function during enteral feeding. Two studies in healthy volunteers aimed to 1) investigate effects of Nutrison Multi Fibre (NMF) on gastrointestinal function, and 2) compare effects of NMF administered orally and nasogastrically on distal colonic motor activity.Methods: (1) Ten subjects were randomly assigned to 3×7 days self-selected diet (SSD), 2 litres Nutrison Standard (NS), or 2 l NMF. Objective and subjective indices were measured. (2) Two groups (n=6) received 2×250 ml boluses of NMF 2 hourly either nasogastrically or orally. Distal colonic motility was measured for 8 h (3 pre/5 post) first bolus.Results: Whole gut transit time was prolonged during NS (P<0.05) compared with SSD or NMF. Stool wet weight was higher during SSD (P<0.05) than during NS or NMF. Bowel frequencies were comparable. NMF was well tolerated. 2. Colonic activity index was maintained after oral administration with no associated diarrhoea. Activity index decreased after nasogastric bolus (P<0.05), but recovered to higher than fasting levels (P<0.05). 5 subjects had watery stools.Conclusions: Oral NMF is well tolerated, normalises whole gut transit time and maintains colonic motility. Recovery of colonic activity after nasogastric bolus suggests a putative protective effect of NMF over a longer period of feeding.

Mice lacking the dopamine transporter display altered regulation of distal colonic motility.

The mechanisms by which dopamine (DA) influences gastrointestinal (GI) tract motility are incompletely understood and complicated by tissue- and species-specific differences in dopaminergic function. To improve the understanding of DA action on GI motility, we used an organ tissue bath system to characterize motor function of distal colonic smooth muscle segments from wild-type and DA transporter knockout (DAT -/-) mice. In wild-type mice, combined blockade of D(1) and D(2) receptors resulted in significant increases in tone (62 +/- 9%), amplitude of spontaneous phasic contractions (167 +/- 24%), and electric field stimulation (EFS)-induced (40 +/- 8%) contractions, suggesting that endogenous DA is inhibitory to mouse distal colonic motility. The amplitudes of spontaneous phasic and EFS-induced contractions were lower in DAT -/- mice relative to wild-type mice. These differences were eliminated by combined D(1) and D(2) receptor blockade, indicating that the inhibitory effects of DA on distal colonic motility are potentiated in DAT -/- mice. Motility index was decreased but spontaneous phasic contraction frequency was enhanced in DAT -/- mice relative to wild-type mice. The fact that spontaneous phasic and EFS-induced contractile activity were altered by the lack of the DA transporter suggests an important role for endogenous DA in modulating motility of mouse distal colon.

Diurnal variation is absent in distal colonic motility following colo-rectal surgery

Diurnal variation is absent in distal colonic motility following colo-rectal surgery

The effects of biofeedback on rectal sensation and distal colonic motility in patients with disorders of rectal evacuation: Evidence of an inhibitory rectocolonic reflex in humans?

OBJECTIVE: Abnormalities of descending colon motility reported in a subset of patients with rectal evacuation disorders are consistent with a rectocolonic inhibitory reflex. Our aims were to evaluate distal colon motor function and rectal sensation in such patients and assess effects of biofeedback (BF) training on these functions. METHODS: Seven patients (five women, two men; mean age 36 yr) with rectal evacuation disorders were studied before and after 10-days biofeedback training; six healthy volunteers (five women, one man; mean age 30 yr) were studied once. Colonic compliance, motility, sensation thresholds, and perception scores during standardized rectal distentions were measured using two barostat-manometry assemblies inserted into the cleansed colon with the aid of flexible sigmoidoscopy. RESULTS: Sigmoid compliance, fasting, and postprandial motility index, and perception thresholds were similar in controls and patients before and after biofeedback training. Postprandial sigmoid tone tended ( p = 0.09) to be lower in patients than controls; after biofeedback, postprandial tone was comparable to that in controls. Rectal urgency scores at 24 mm Hg distention were greater in patients than in controls ( p = 0.02 for both). After biofeedback, there were trends for lower perceptions of urgency to defecate (7.6 ± 1.1 cm pre- vs 5.3 ± 1.5 post-; p = 0.04) at 24 mm Hg; conversely, gas sensation at 12 mm Hg was higher (1.2 ± 0.5 cm pre- vs 3.3 ± 0.6 post-; p = 0.05). CONCLUSIONS: Normalization of rectal evacuation and postprandial sigmoid tone in patients with evacuation disorders by biofeedback training supports the presence of a rectocolonic inhibitory reflex. Effect of biofeedback on rectal sensation in these patients requires further study.

The effects of biofeedback on rectal sensation and distal colonic motility in patients with disorders of rectal evacuation: evidence of an inhibitory rectocolonic reflex in humans?

Abnormalities of descending colon motility reported in a subset of patients with rectal evacuation disorders are consistent with a rectocolonic inhibitory reflex. Our aims were to evaluate distal colon motor function and rectal sensation in such patients and assess effects of biofeedback (BF) training on these functions. Seven patients (five women, two men; mean age 36 yr) with rectal evacuation disorders were studied before and after 10-days biofeedback training; six healthy volunteers (five women, one man; mean age 30 yr) were studied once. Colonic compliance, motility, sensation thresholds, and perception scores during standardized rectal distentions were measured using two barostat-manometry assemblies inserted into the cleansed colon with the aid of flexible sigmoidoscopy. Sigmoid compliance, fasting, and postprandial motility index, and perception thresholds were similar in controls and patients before and after biofeedback training. Postprandial sigmoid tone tended (p = 0.09) to be lower in patients than controls; after biofeedback, postprandial tone was comparable to that in controls. Rectal urgency scores at 24 mm Hg distention were greater in patients than in controls (p = 0.02 for both). After biofeedback, there were trends for lower perceptions of urgency to defecate (7.6 +/- 1.1 cm pre- vs 5.3 +/- 1.5 post-; p = 0.04) at 24 mm Hg; conversely, gas sensation at 12 mm Hg was higher (1.2 +/- 0.5 cm pre- vs 3.3 +/- 0.6 post-; p = 0.05). Normalization of rectal evacuation and postprandial sigmoid tone in patients with evacuation disorders by biofeedback training supports the presence of a rectocolonic inhibitory reflex. Effect of biofeedback on rectal sensation in these patients requires further study.

Motor responses elicited by local electrical stimulation of the distal colon in the anaesthetized rat.

A method to study electrically induced distal colonic motility in the rat in vivo is reported. The animals were anaesthetized with methohexital and chloralose and were artificially ventilated. Motility of a segment (2 cm) of the distal colon was monitored as volume changes of an intraluminal balloon, introduced via the anus. Local electrical stimulation of the wall of the segment was achieved by means of a bipolar electrode folded around the gut. Stimulations produced reproducible contractile responses in a frequency dependent fashion. Stimulation characteristics resembled those of other autonomic neuro-effector systems. The adrenergic neuron-blocker, guanethidine, significantly lowered colonic tone, but had no other effects on spontaneous or electrically induced motility. Atropine significantly lowered colonic tone. After the administration of this compound the electrically induced contractions were significantly smaller with a shorter duration and, furthermore, appeared upon the cessation of stimulation ('off' or 'rebound' contraction). Following the administration of tetrodotoxin (TTX, given close i.a. via a cannula with its tip in distal aorta) basal colonic tone and the number of spontaneously occurring contractions increased. The amplitude and duration of the electrically induced responses were significantly attenuated and, furthermore, appeared as 'rebound' contractions which were preceded by a relaxation. Such TTX-resistant responses may be myogenic, but a neurogenic origin cannot be excluded. The present study showed that local electrical stimulation of the distal colon elicits cholinergic contractions, but also atropine- and TTX-resistant motor responses.

Does a nasogastric tube adversely affect distal colonic motility and contribute to pathogenesis of enteral feeding-related diarrhea?

Does a nasogastric tube adversely affect distal colonic motility and contribute to pathogenesis of enteral feeding-related diarrhea?

Characterization of 5-hydroxytryptamine (5-HT) receptor subtypes influencing colonic motility in conscious dogs.

We examined the effects of exogenous 5-hydroxytryptamine (5-HT) and selective 5-HT receptor agonists and antagonists on proximal, middle and distal colonic motility in conscious fasted dogs with extraluminal force transducers implanted chronically. 5-HT (0.003-0.1 mg/kg i.v.) dose-dependently enhanced motility along the entire length of the colon. The 5-HT (0.03 mg/kg i.v.)-induced response was inhibited by 0.1-1.0 mg/kg i.v. methysergide, a 5-HT1/2 antagonist, at all recording sites and by 0.1-1.0 mg/kg i.v. ketanserin, a 5-HT2A antagonist, at the middle and distal sites only. At 1 mg/kg i.v., YM060, a 5-HT3 antagonist, reduced the amplitude of the initial transient high-amplitude contractions induced by 5-HT, but did not affect the tonic contraction induced by 5-HT. At doses up to 3 mg/kg i.v., 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino) ethyl ester (SDZ205-557), a 5-HT4 antagonist, and hexamethonium (up to 10 mg/kg i.v.) did not affect 5-HT-induced responses at any recording site. Renzapride, a 5-HT4 agonist, also stimulated motility along the entire length of the colon at 0.3 mg/kg i.v.. The renzapride-induced response was inhibited by 1 mg/kg i.v. SDZ205-557 or 3 mg/kg i.v. hexamethonium. m-Chlorophenylbiguanide (m-CPBG), a 5-HT3 agonist, (1 mg/kg i.v.) produced a transient high-amplitude contraction at all recording sites and this contraction was eliminated by pretreatment with 0.03 mg/kg i.v. YM060. The contraction produced by m-CPBG declined rapidly, so the increase in the motility index by m-CPBG was not significant at any recording site. Of the antagonists tested, 0.1-1 mg/kg i.v. methysergide produced a delayed and prolonged contractile response at the middle and distal sites. The onset of the response was delayed about 20 min after application and the response was maintained over the subsequent 60-min observation period. The methysergide (1 mg/kg i.v.)-induced response was inhibited by 3 mg/kg i.v. hexamethonium. The other antagonists, ketanserin, YM060 and SDZ205-557, had no contractile effect at any recording site. These results indicate that exogenous 5-HT stimulates motility along the entire length of the fasted canine colon and that 5-HT-induced responses in the proximal colon are mediated mainly by 5-HT1, whereas those in the middle and distal colon are mediated by both 5-HT1 and 5-HT2 receptors. Renzapride and methysergide also stimulate colonic motility via additional mechanisms. The activation of 5-HT4 receptors and the blockade of endogenous 5-HT inhibitory regulation via 5-HT1 receptors may be involved in the action of renzapride and methysergide respectively.

Involvement of endogenous nitric oxide in the regulation of distal colonic motility in anaesthetized rat

Involvement of endogenous nitric oxide in the regulation of distal colonic motility in anaesthetized rat

Effects of purified Clostridium difficile toxin A on rabbit distal colon

Background & Aims: Antibiotic-associated pseudomembranous colitis in humans is caused by proliferation of Clostridium difficile, which elaborates an enterotoxin toxin A that causes epithelial damage and altered motility in rabbit small intestine. The aim of this study was to assess the effects of toxin A on rabbit distal colonic motility and to relate this to histological damage and inflammatory mediator production. Methods: Two hundred micrograms per milliliter of toxin A was placed in a distal colonic loop in anesthetized rabbits, and myoelectric activity was recorded for the following 7 hours. The colon was histologically evaluated and assayed for eicosanoid production. The effects of toxin A on longitudinal and circular muscle were also assessed in vitro. Results: Beginning 1 hour after instillation, toxin A caused a significant increase in the number of spike bursts without altering slow wave frequency; this was associated with an increase in mucosal neutrophils and increased production of prostaglandin E 2 and leukotrienes B 4 and C 4/D 4/E 4. Seven hours after administration of toxin A, mediator levels and myoelectric activity remained increased but significant mucosal damage was now also present. Toxin A did not affect longitudinal or circular muscle in vitro. Conclusions: C. difficile toxin A caused a significant neutrophil infiltration and an increased myoelectric activity before producing mucosal damage. The myoelectric effect may be indirect, resulting from the production of motility-altering arachidonic acid metabolites.

Whorwell et al's “Physiological Effects of Emotion: Assessment Via Hypnosis”

“Assessment of the physiological effects of physical and emotional stress has been hampered by a lack of suitable laboratory techniques. Since hypnosis can be used safely to induce specific emotional states of considerable intensity, we studied the effect on distal colonic motility of three hypnotically induced emotions (excitement, anger, and happiness) in 18 patients aged 20–48 years with irritable bowel syndrome. Colonic motility index was reduced by hypnosis on its own (mean change 19.1; 95% CI 0.8, 37.3; P &lt; 0.05) and this change was accompanied by decreases in both pulse (12; 8, 15) and respiration (6; 4, 8) rates (P &lt; 0.001 for both). Anger and excitement increased the colonic motility index (50.8; 29.4, 72.2; and 30.4; 8.9, 51.9, respectively; P &lt; 0.01 for both), pulse rate (26; 22, 30; and 28; 24, 32; P &lt; 0.001 for both), and respiration rate (14; 12, 16; and 12; 10, 14; P &lt; 0.001 for both). Happiness further reduced colonic motility although not significantly from that observed during hypnosis alone. Changes in motility were mainly due to alterations in rate than in amplitude of contractions. Our results indicate that hypnosis may help in the investigation of the effects of emotion on physiological functions; this approach could be useful outside the gastrointestinal system. Our observation that hypnosis strikingly reduces fasting colonic motility may partly explain the beneficial effects of this form of therapy in functional bowel disorders.”

Physiological effects of emotion: assessment via hypnosis

Assessment of the physiological effects of physical and emotional stress has been hampered by a lack of suitable laboratory techniques. Since hypnosis can be used safely to induce specific emotional states of considerable intensity, we studied the effect on distal colonic motility of three hypnotically induced emotions (excitement, anger, and happiness) in 18 patients aged 20-48 years with irritable bowel syndrome.Colonic motility index was reduced by hypnosis on its own (mean change 19·1; 95% Cl 0·8, 37·3; p<0·05) and this change was accompanied by decreases in both pulse (12; 8, 15) and respiration (6; 4, 8) rates (p<0·001 for both). Anger and excitement increased the colonic motility index (50·8; 29·4, 72·2; and 30·4; 8·9, 51·9, respectively; p<0·01 for both), pulse rate (26; 22, 30; and 28; 24, 32; p<0·001 for both), and respiration rate (14; 12, 16; and 12; 10, 14; p<0·001 for both). Happiness further reduced colonic motility although not significantly from that observed during hypnosis alone. Changes in motility were mainly due to alterations in rate than in amplitude of contractions.Our results indicate that hypnosis may help in the investigation of the effects of emotion on physiological functions; this approach could be useful outside the gastrointestinal system. Our observation that hypnosis strikingly reduces fasting colonic motility may partly explain the beneficial effects of this form of therapy in functional bowel disorders.

Modulation of colonic motility by substance P, cholecystokinin and neuropeptide Y

The effects of substance P, cholecystokinin and neuropeptide Y were examined on rabbit distal colonic motility. All three agents produced increased contractile activity but the mechanisms responsible differed depending on the agent tested. In the intact animal, peptide effects were measured under basal conditions and following exposure to atropine, tetrodotoxin and the alpha-adrenergic antagonist phentolamine. Administration of all three peptides resulted in a stimulation of colonic motility. Phentolamine did not significantly effect substance P-, cholecystokinin- or neuropeptide Y-induced activity. By contrast, the in vivo activity induced by cholecystokinin and neuropeptide Y, but not substance P, was nearly eliminated by tetrodotoxin. Only the neuropeptide Y response was partially atropine sensitive. In isolated colonic strips, cholecystokinin-induced activity, but not that produced by neuropeptide Y or substance P, was blocked by tetrodotoxin. Atropine did not significantly inhibit any of the hormone-induced contractions.

Recovery from disturbed colonic transit time after alcohol withdrawal

The effects of alcohol withdrawal on total and segmental transit time were evaluated in 20 chronic alcoholic subjects. After withdrawal, colorectal transit time significantly increased from 24.9 +/- 3.6 to 33.3 +/- 4.5 hours mean +/- SE (P less than 0.01). This was the result of an exclusive increase in rectosigmoid transit time from 2.8 +/- 0.7 to 9.8 +/- 2.1 hours (P less than 0.001). No variations were found in right or left colon transit time. Distal colonic motility is thus a crucial factor in the genesis of diarrhea in chronic alcoholic subjects.

Effect of Hyperventilation on Distal Colonic Motility and Rectal Sensitivity in Irritable Bowel Syndrome

Hyperventilation is associated with some symptoms suggestive of irritable bowel syndrome and has been implicated in provoking excessive oesophageal contractility. Sixteen patients with irritable bowel syndrome were therefore studied in order to assess the effect of hyperventilation on distal colonic motility and rectal sensitivity. No significant change in either the amplitude or frequency of colonic contractile activity was noted following hyperventilation, nor was any alteration in rectal sensitivity observed. This study shows that acute hyperventilation does not affect colonic motor activity or visceral sensitivity and suggests that hyperventilation and irritable bowel syndrome are not causally related.