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Symptom overlap and comorbidity of irritable bowel syndrome with other conditions.

Irritable bowel syndrome (IBS) is one of several highly prevalent, multi-symptom gastrointestinal motility disorders that have a wide clinical spectrum and are associated with symptoms of gastrointestinal dysmotility and visceral hypersensitivity. Symptom overlap and comorbidity between IBS and other gastrointestinal motility disorders (eg, chronic constipation, functional dyspepsia, gastroesophageal reflux disease), with gastrointestinal disorders that are not related to motility (eg, celiac disease, lactose intolerance), and with somatic conditions (eg, fibromyalgia, chronic fatigue syndrome), are frequent. The clinical associations and pathophysiologic links between IBS and these disorders continue to be explored. This review discusses overlapping symptoms and comorbidity of IBS with select gastrointestinal and non-gastrointestinal disorders and attempts to identify commonalities among these conditions.

Celiac Disease↗

Protection by the calcium antagonist Wy-47,037 against stress ulceration in the rat.

Wy-47,037, a novel compound with both intracellular and extracellular calcium-blocking properties, was evaluated for its effects on cold/restraint stress induced ulceration in the rat. Wy-47,037 dose-dependently inhibited ulcerogenesis; with an ED50 of 8 mg/kg, PO, it was approximately twice as potent as nitrendipine (ED50 = 15 mg/kg). Wy-47,037 also reduced basal gastric acid secretion (ED50 = 7 mg/kg) and gastrointestinal motility (ED50 = 16 mg/kg). It is thus possible that Wy-47,037's alteration of basal gastric acid secretion and/or of gastrointestinal motility may contribute to its therapeutic efficacy against stress induced ulcer formation.

Animals↗

Antidiarrhoeal activity of the ethanol extract of Paederia foetida Linn. (Rubiaceae).

Paederia foetida L. is used as a remedy for diarrhoea and dysentery in Asia, but has not been investigated for its antidiarrhoeal properties. Antidiarrhoeal activity of 90% ethanol extract of Paederia foetida was investigated in this study using castor oil and magnesium sulphate-induced diarrhoea models in mice. The extract significantly increased the latent period of diarrhoea in both the models. In the castor oil study, the purging index (PI) value lowered in 1 h of the study at (100, 250 and 500 mg/kg) doses. The effect continued up to 6-h period only at 500 mg/kg dose. The plant notably reduced the purging index value in a dose-dependent manner in magnesium sulphate-induced diarrhoea. Paederia foetida, in general, reduced the gastrointestinal motility with barium sulphate milk both in 15- and 30-min time intervals. The extract significantly decreased the cisplatin-induced gastrointestinal motility at all doses at both time intervals. The extract also enhanced the morphine-induced reduction of motility at 500 mg/kg dose level at both time intervals. The results suggest that Paederia foetida showed antidiarrhoeal activity by inhibiting intestinal motility and justify its use in traditional medicine.

Animals↗

Prokinetic agents.

Prokinetic agents are medications that promote gastrointestinal motility. This article reflects the current state of our understanding of their mechanisms of action and their clinical utility in treating disorders of gastrointestinal motility, including gastroesophageal reflux, gastroparesis, small-intestinal dysmotility, and constipation.

Benzamides↗

[Treatment of upper-abdominal pain in chronic gastritis. Results of therapy with the motility regulating drug Bromopride].

After discussing the aetiological role of the reflux from the duodenum in causing and maintenance of chronic gastritis, the author studied the effect of bromopride, a drug regulating gastrointestinal motility, on the subjective complaints of individuals suffering from the disease. In a randomized double-blind trial, 31 subjects with upper abdominal complaints, histologically established antrum gastritis and endoscopic signs for disorders of pyloric function were treated with one capsule three times daily of bromopride or a placebo, over a period of three weeks. The positive therapeutic results in 12 of 13 patients on bromopride provide support for the clinical use of a drug regulating gastrointestinal motility in the treatment of duodeno-gastric reflux causing the discomfort of individuals with chronic gastritis. Subjects exhibiting a sensation of fullness and pressure, flatulence, pain in the epigastrium and eructations, were found to be most responsive to bromopride. No relationship between side-effects and drug treatment was observed.

Abdomen↗

[Y1 receptors mediate inhibitory and stimulatory effects of peptide YY in isolated small intestine and large intestine muscles of the rabbit].

Peptide YY has been shown to have stimulatory and inhibitory effects on gastrointestinal motility. However, the receptors mediating these effects are unknown. To determine if specific YY receptor agonists can mediate the effects on gastrointestinal motility we studied the effects of peptide YY (PYY), of Pro34PYY, a selective Y1 agonist, and of PYY 3-36, a selective Y2 agonist, on the motility in isolated smooth muscle strips from rabbit small and large intestine. In strips from distal colon, PYY stimulated spontaneous motility whereas it inhibited spontaneous contractions in circular strips from distal ileum. In distal circular colon maximal inotropic response (10.1 +/- 2.1% of a maximal response to carbachol 10(-5) M) was found at PYY 10(-8) M; (ED50 3.1 +/- 1.2 x 10(-9) M). In distal circular ileum maximal inhibition (by 39 +/- 20% of basal motility index) was found at 10(-7) M; (ID50 6.2 +/- 1.4 x 10(-9) M). PYY caused a dose-dependent inhibition of the on-contraction induced by electrical field stimulation. This inhibition could not be reversed by alpha- or beta-adrenergic blockade. PYY had no influence on the inotropic response evoked by carbachol. Both the stimulatory effect of PYY observed in distal colon and the inhibitory effect in distal ileum could be reproduced by the Y1 agonist Pro34PYY, but not by the Y2 agonist PYY 3-36. In distal circular colon the maximal inotropic response evoked by the Y1 agonist was 10 +/- 1.4%; (ED50 1.2 +/- 0.5 x 10(-8) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Leuprolide acetate affects intestinal motility in female rats before and after ovariectomy.

Leuprolide acetate, a gonadotropin-releasing hormone (GnRH) analogue, is currently being proposed to control debilitating symptoms in women with functional bowel disease. Whether leuprolide alters gastrointestinal motility as part of its actions is unknown. This study was designed to assess, using myoelectric techniques in an animal model, the effects of leuprolide on potential mechanisms of neuromuscular function of small intestine. Female rats with (n = 6) or without (n = 8) bilateral ovariectomy were used to study jejunal motility before and after leuprolide therapy. Throughout the study, daily leuprolide dosages of 0.02, 0.2, or 0.4 micrograms/kg were injected into intact rats and 0.02, 0.2, 0.4, 1.0, or 2.5 micrograms/kg into ovariectomized rats. Recordings were made while the rats were fasted and postprandial and before and after leuprolide administration. Under control conditions, migrating myoelectric complexes (MMCs) were found in intact female rats, whether fasted or postprandial. After ovariectomy, postprandial controls and those treated with low-dose leuprolide (0.02, 0.2, and 0.4 micrograms) had typical fed-state patterns and no MMCs, but at 1.0 and 2.5 micrograms the fed state was inhibited and cycling MMCs occurred at a frequency similar to that of fasted controls. Reproductive hormones thus have a significant effect on gastrointestinal motility.

Animals↗

Dissociation of analgesic and gastrointestinal effects of electroconvulsive shock-released opioids.

Activation of endogenous opioid systems by electroconvulsive shock (ECS) produced naloxone-reversible thermal analgesia (52 degrees C hot plate) 5 min after ECS administration. Although opioid peptides injected intracerebroventricularly have previously been found to inhibit gastrointestinal motility, ECS treatment did not affect gastric emptying, small or large intestinal transit. These results suggest that centrally-mediated opioid analgesia and changes in gastrointestinal motility are initiated through independent mechanisms.

Animals↗

A diterpenoid from Salvia cinnabarina inhibits mouse intestinal motility in vivo.

This study was aimed to investigate the effect of 3,4 secoisopimara-4(18),7,15-trien-3-oic acid (compound 1) isolated from the aerial parts of Salvia cinnabarina, on upper gastrointestinal transit in mice in vivo. Compound 1 (10 - 100 mg/kg, i. p.) dose-dependently delayed gastrointestinal motility. Pretreatment ( i. p.) of mice with hexamethonium (10 mg/kg), naloxone (2 mg/kg), N(G)-nitro- L-arginine-methyl ester ( L-NAME) (25 mg/kg) or yohimbine (1 mg/kg) did not modify the inhibitory effect of compound 1 (50 mg/kg). However, the L-type Ca (2+) channel verapamil (5 mg/kg, i. p.) significantly reduced the antimotility effect of compound 1 (50 mg/kg). These results suggest that compound 1 inhibits gastrointestinal motility in mice. The effect could involve, at least in part, L-type Ca (2+) channels.

Animals↗

Delayed gastrointestinal transit times in anorexia nervosa and bulimia nervosa.

Anorectic and bulimic patients frequently report symptoms of constipation, bloating, and abdominal pain suggestive of abnormal gastrointestinal motility or transit. However, except for studies of gastric emptying, gastrointestinal motility and transit in these eating disorders have not been investigated. Ten anorectic and 18 bulimic inpatients were compared with 10 healthy controls. Whole-gut transit was tested by the radiopaque marker technique, and mouth-to-cecum transit time was assessed by the lactulose breath test. All anorectics and 67% of bulimics complained of constipation. Whole-gut transit time was significantly delayed in both anorectics (66.6 +/- 29.6 hours) and bulimics (70.2 +/- 32.4 hours) compared with controls (38.0 +/- 19.6 hours). Mouth-to-cecum transit time also tended to be longer in anorectics (109.0 +/- 33.5 minutes) and bulimics (106.2 +/- 24.5 minutes) than in controls (84.0 +/- 27.7 minutes), but these differences were not statistically significant. Delayed transit could contribute to or perpetuate the eating disorders by (a) causing the patient to feel bloated, thereby exacerbating fear of fatness, or (b) causing rectal distention, which may reflexly inhibit gastric emptying.

Adolescent↗

Enteric neuropathology: recent advances and implications for clinical practice.

Because of their high prevalence in clinical practice, the field of gastrointestinal motility has tended to focus its clinical and research efforts on such functional disorders as nonulcer dyspepsia, the irritable bowel syndrome, and functional constipation. Because these disorders are difficult to define and their diagnosis remains exclusively symptomatic, progress has been difficult in these areas, and advances in clinical gastrointestinal motility generally have been hampered. This review attempts to emphasize the prevalence and importance of "organic" motility disorders, ie, those disorders of gastrointestinal motor dysfunction that are to a greater or lesser extent based on defined pathology and pathophysiology. Although some of these disorders are rare, recent dramatic progress has important lessons for motility in general and should point the way toward a greater understanding of the more common motor disorders.

Autonomic Nervous System Diseases↗

Effect of somatostatin on gastrointestinal contractility in Schistosoma mansoni infected mice.

Schistosoma mansoni infection induces severe gastrointestinal motility disturbances which are characterised by hyperactivity of intestinal muscle, abdominal pain, diarrhoea, vomiting and nausea. During schistosomiasis, the neuropeptide somatostatin is generated within inflammatory granulomas. However, somatostatin is also an important inhibitory modulator of gastrointestinal motility. In the present study, we have investigated the potential of somatostatin to reduce schistosomiasis-induced hyperactivity of gastrointestinal smooth muscle. Organ bath experiments were performed to study the contractility of isolated smooth muscle strips of intestine from control mice and from mice that were infected with S. mansoni for 2, 4, 8 and 16 weeks. Electrical field stimulation (0.5-8 Hz) of enteric nerves induced frequency-dependent neurogenic contractions of cholinergic origin in all regions of the small intestine. Somatostatin (0.1-1 microM) concentration-dependently inhibited the contractions to enteric nerve stimulation in the small intestine from uninfected control mice and from acutely S. mansoni infected mice (2 and 4 weeks of infection). After 8 weeks of infection with S. mansoni, this inhibitory effect of somatostatin was less pronounced and after 16 weeks of infection it was completely abolished. Histology demonstrated that chronic infection of mice with S. mansoni was associated with significant alterations in the musculature of the small intestine. These alterations may be associated with physiological changes in the responsiveness to somatostatin and suggest that the somatostatin neuroregulatory circuit of enteric neurotransmission in the small intestine is disturbed during chronic schistosomiasis mansoni.

Animals↗

Nonmigrating rhythmic activity in the stomach and duodenum of neonates.

We studied gastrointestinal motility in 20 infants, using a modified manometric method for neonates, and compared it to that in adults. Changes in the intragastric and intraduodenal pressures were recorded for 3 h after the ingestion of milk. Bands of contractions with the same rhythmicity as phase III activity in adults were frequently recorded. Some of them migrated caudally and were speculated to the equivalent of phase III activity of the interdigestive migrating complex (IMC) in adults. However, others did not migrate and showed some differences from phase III activity of adults and infants in the time of occurrence, duration and amplitude. The characteristic of gastroduodenal motility in infants was the frequent occurrence of these bands of nonmigrating rhythmic concentrations. Our findings indicated the following problems: (1) there are some differences in gastrointestinal motility between infants and adults and further investigations are required for the evaluation of the physiology or pathophysiology of this phenomenon; (2) in infants, many bands of rhythmic contractions of the alimentary tracts can exist without migration. This indicates the possibility that the occurrence of rhythmic contractions and their migration are regulated by different mechanisms.

Adult↗

Neuronal nitric oxide synthase is necessary for elimination of Giardia lamblia infections in mice.

NO produced by inducible NO synthase (NOS2) is important for the control of numerous infections. In vitro, NO inhibits replication and differentiation of the intestinal protozoan parasite Giardia lamblia. However, the role of NO against this parasite has not been tested in vivo. IL-6-deficient mice fail to control Giardia infections, and these mice have reduced levels of NOS2 mRNA in the small intestine after infection compared with wild-type mice. However, NOS2 gene-targeted mice and wild-type mice treated with the NOS2 inhibitor N-iminoethyl-L-lysine eliminated parasites as well as control mice. In contrast, neuronal NOS (NOS1)-deficient mice and wild-type mice treated with the nonspecific NOS inhibitor NG-nitro-L-arginine methyl ester and the NOS1-specific inhibitor 7-nitroindazole all had delayed parasite clearance. Finally, Giardia infection increased gastrointestinal motility in wild-type mice, but not in SCID mice. Furthermore, treatment of wild-type mice with NG-nitro-L-arginine methyl ester or loperamide prevented both the increased motility and the elimination of parasites. Together, these data show that NOS1, but not NOS2, is necessary for clearance of Giardia infection. They also suggest that increased gastrointestinal motility contributes to elimination of the parasite and may also contribute to parasite-induced diarrhea. Importantly, this is the first example of NOS1 being involved in the elimination of an infection.

Animals↗

Gastric and small intestinal myoelectric dysrhythmia associated with chronic intractable nausea and vomiting.

We describe a patient with symptoms of severe nausea, vomiting, epigastric bloating and pain, and marked weight loss due to a gastrointestinal motility disturbance. Motility abnormalities were characterized by uncoordinated high pressure (as high as 300 mm Hg) contractions and uncoordinated interdigestive motor complexes in the duodenum and small intestine, and tachygastria often associated with tachyarrhythmia in the gastric myoelectric activity recordings. Uncoordinated interdigestive myoelectric complexes again were found in the duodenum and small intestine. These abnormal myoelectric activities observed in the in-vivo study were confirmed in the in-vitro study. After distal hemigastrectomy and gastrojejunostomy, the symptoms of nausea, vomiting, and epigastric pain decreased considerably. Thus, the motility abnormality found in the study appears to be responsible for the symptoms described. This is probably a new clinical entity. The importance of manometric and myoelectric study of a gastrointestinal motility for unexplained nausea and vomiting is emphasized.

Adult↗

The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs.

BACKGROUND: The herbal medicine Dai-Kenchu-To, composed of zanthoxylum fruit, ginseng root, and dried ginger rhizome, is clinically effective for uncomplicated postoperative adhesive intestinal obstruction. We investigated the effect of Dai-Kenchu-To and each ingredient on upper gastrointestinal motility and its mechanism of action. METHODS: Five mongrel dogs were equipped with 4-strain gauge-force transducers on the gastric body, antrum, duodenum, and jejunum to measure contractile activity of the circular muscle. Dai-Kenchu-To (1.5 g) or the separate ingredients zanthoxylum fruit, ginseng root, or dried ginger rhizome (1.0 g each) were administered by bolus into the gastric lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intragastric Dai-Kenchu-To-induced contractions was studied. RESULTS: Intragastric Dai-Kenchu-To induced phasic contractions in the antrum, duodenum, and jejunum. Zanthoxylum fruit elicited phasic contractions mainly in the duodenum and jejunum, whereas dried ginger rhizome induced phasic contractions in the antrum. Ginseng root had no effect. Phasic contractions induced by intragastric Dai-Kenchu-To were inhibited by atropine and hexamethonium at all sites, although ondansetron inhibited these contractions in the antrum and duodenum. CONCLUSIONS: Intragastric Dai-Kenchu-To stimulates upper gastrointestinal motility through cholinergic and 5-hydroxytryptamine 3 receptors.

Animals↗

Antroduodenal manometry in children with no upper gastrointestinal symptoms.

BACKGROUND: The interpretation of antroduodenal manometry in children with gastrointestinal motility disorder has been limited by a paucity of data from normal children. The purpose of this study was to define antroduodenal manometry findings in children with no upper gastrointestinal symptoms. METHODS: We reviewed 260 consecutive antroduodenal manometries and selected 18 studies from subjects aged 2-12 years with no symptoms referable to a gastrointestinal motility disorder involving the stomach and/or the small bowel. RESULTS: During fasting, phase 3 of the migrating motor complex (MMC) was present in 14 of 18 children, and it was induced by erythromycin in 4 who failed to have a spontaneous phase 3. Phase 3 propagation velocity increased significantly with age. The cycle length between MMCs showed no age-dependent variation. Phase 3 occupied 3%; phase 1, 10%; and phase 2, 87% of the fasting recording time. CONCLUSIONS: Antroduodenal manometry findings in children with no upper gastrointestinal symptoms are similar to those in adults.

Adult↗

Intraduodenal and intrajejunal administration of the herbal medicine, dai-kenchu-tou, stimulates small intestinal motility via cholinergic receptors in conscious dogs.

The aim of the present study was to study the effect and mechanism of action of intraduodenal and intrajejunal dai-kenchu-to, an herbal medicine clinically effective for uncomplicated postoperative adhesive intestinal obstruction, on upper gastrointestinal motility. Five mongrel dogs were equipped with four strain-gauge force transducers on the antrum, duodenum, and proximal and distal jejunum to measure contractile activity. Dai-kenchu-to (0.5, 1.5, and 3.0 g) was administered into the duodenal or proximal jejunal lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intraduodenal and intrajejunal dai-kenchu-to-induced contractions was studied. Plasma motilin was measured by specific radioimmunoassay. Intraduodenal and intrajejunal dai-kenchu-to induced phasic contractions in the duodenum and proximal jejunum, respectively, and those contractions migrated distally. Phasic contractions induced by intraduodenal and intrajejunal dai-kenchu-to were inhibited by atropine and hexamethonium at all sites. Plasma motilin was not affected by dai-kenchu-to. Intraduodenal and intrajejunal dai-kenchu-to stimulates upper gastrointestinal motility at and distal to the administration sites through cholinergic receptors.

Animals↗