Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In contrast to irritable bowel syndrome (IBS), the prevalence and risk factors for diarrhoea in the absence of IBS in the community are unknown. We aimed to evaluate potential risk factors for chronic diarrhoea (non-IBS). A valid questionnaire that recorded gastrointestinal symptoms required for a diagnosis of chronic diarrhoea, self-reported measures of potential risk factors, and a somatic symptom checklist was mailed to an age- and gender-stratified random sample of Olmsted County, Minnesota residents (30-64 year). Chronic diarrhoea was defined as reporting one or more of the following symptoms more than 25% of the time in the past 3 months: > or =3 bowel movements a day, loose or watery stools, or faecal urgency. Subjects with IBS (Rome III) were excluded. Of 892 eligible subjects, 653 (73%) responded. Among 523 respondents not reporting IBS, chronic diarrhoea was reported by 148 (28%); 90 (61%) had chronic painless diarrhoea. Chronic diarrhoea was significantly associated with self-reported food sensitivity (OR = 2.05 [1.31-3.20]) and stress (OR = 1.99 [1.03-3.85]). Both remained significant in the adjusted variable models that excluded subjects with any abdominal pain. Female gender (OR = 0.67 [0.45-0.98]) and higher education level (OR = 0.60 [0.39-0.92]) had smaller odds for chronic diarrhoea. No association was detected for age, marital status, body mass index, cigarette or alcohol use, coffee, analgesics, emotional support, pets or water source. Chronic diarrhoea in the absence of IBS is common; self-reported food sensitivity, male gender and a lower level of education are risk factors.
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PMID:Risk factors for chronic diarrhoea in the community in the absence of irritable bowel syndrome. 1946 Jan 5

To investigate the possible contribution of peripheral sensory mechanisms to abdominal pain following infectious colitis, we examined whether the Citrobacter rodentium mouse model of human E. coli infection caused hyperexcitability of nociceptive colonic dorsal root ganglion (DRG) neurons and whether these changes persisted following recovery from infection. Mice were gavaged with C. rodentium or distilled water. Perforated patch clamp recordings were obtained from acutely dissociated Fast Blue labelled colonic DRG neurons and afferent nerve recordings were obtained from colonic afferents during ramp colonic distensions. Recordings were obtained on day 10 (acute infection) and day 30 (infection resolved). Following gavage, colonic weights, myeloperoxidase (MPO) activity, stool cultures, and histological scoring established that infection caused colitis at day 10 which resolved by day 30 in most tissues. Electrophysiological recordings at day 10 demonstrated hyperexcitability of colonic DRG neurons (40% mean decrease in rheobase, P = 0.02; 50% mean increase in action potential discharge at twice rheobase, P = 0.02). At day 30, the increase in action potential discharge persisted (approximately 150% increase versus control; P = 0.04). In voltage clamp studies, transient outward (I(A)) and delayed rectifier (I(K)) currents were suppressed at day 10 and I(A) currents remained suppressed at day 30. Colonic afferent nerve recordings during colonic distension demonstrated enhanced firing at day 30 in infected animals. These studies demonstrate that acute infectious colitis evokes hyperexcitability of colonic DRG neurons which persists following resolution of the infection and that suppression of I(A) currents may play a role. Together, these findings suggest that peripheral pain mechanisms could contribute to post-infectious symptoms in conditions such as post-infectious irritable bowel syndrome.
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PMID:Citrobacter rodentium colitis evokes post-infectious hyperexcitability of mouse nociceptive colonic dorsal root ganglion neurons. 1947 Jul 77

Patients with irritable bowel syndrome (IBS) show decreased discomfort and pain thresholds to visceral stimuli, as well hypervigilance to gastrointestinal sensations, symptoms, and the context in which these visceral sensations and symptoms occur. Previous research demonstrated normalization of visceral hypersensitivity following repeated exposure to experimental rectal stimuli over a 12-month period that was associated with reduction in cortical regions functionally associated with attention and arousal. Building upon these functional analyses, multivariate functional and effective connectivity analyses were applied to [(15)O] water positron emission tomography (PET) data from 12 IBS patients (male=4) participating in a PET study before and after 4 visceral sensory testing sessions involving rectal balloon distensions over a 1-year period. First, behavioral partial least squares was applied to test for networks related to reduced subjective ratings observed following repeated application of an aversive rectal stimulus. Next, path analysis within a structural equation modeling framework tested the hypothesis that perceptual habituation to the repeated visceral stimuli resulted in part from the reduced connectivity within a selective attention to threat network over time. Two independent, perception-related networks comprised of interoceptive, attentional and arousal regions were engaged differentially during expectation and distension. In addition, changes in the effective connectivity of an attentional network as well as modulatory amygdala influence suggested that perceptual habituation associated with repeated stimulus delivery results both in an increase in top-down modulation of attentional circuits, as well as in a reduction of amygdala-related interference with attentional mechanisms.
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PMID:Brain networks underlying perceptual habituation to repeated aversive visceral stimuli in patients with irritable bowel syndrome. 1950 Nov 73

Irritable bowel syndrome is in part characterized by an increased sensitivity to colonic distension. Stress is an important trigger factor for symptom generation. We hypothesized that stress induces visceral hypersensitivity via mast cell degranulation and transient receptor ion channel 1 (TRPV1) modulation. We used the rat model of neonatal maternal separation (MS) to investigate this hypothesis. The visceromotor response to colonic distention was assessed in adult MS and non-handled (NH) rats before and after acute water avoidance (WA) stress. We evaluated the effect of the mast cell stabilizer doxantrazole, neutralizing antiserum against the mast cell mediator nerve growth factor (NGF) and two different TRPV1 antagonists; capsazepine (non-specific) and SB-705498 (TRPV1-specific). Immunohistochemistry was used to assess post-WA TRPV1 expression in dorsal root ganglia and the presence of immunocytes in proximal and distal colon. Retrograde labelled and microdissected dorsal root ganglia sensory neurons were used to evaluate TRPV1 gene transcription. Results showed that acute stress induces colonic hypersensitivity in MS but not in NH rats. Hypersensitivity was prevented by prestress administration of doxantrazole and anti-NGF. Capsazepine inhibited and SB-705498 reversed poststress hypersensitivity. In MS rats, acute stress induced a slight increase in colonic mast cell numbers without further signs of inflammation. Post-WA TRPV1 transcription and expression was not higher in MS than NH rats. In conclusion, the present data on stress-induced visceral hypersensitivity confirm earlier reports on the essential role of mast cells and NGF. Moreover, the results also suggest that TRPV1 modulation (in the absence of overt inflammation) is involved in this response. Thus, mast cells and TRPV1 are potential targets to treat stress-induced visceral hypersensitivity.
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PMID:Essential role for TRPV1 in stress-induced (mast cell-dependent) colonic hypersensitivity in maternally separated rats. 1952 46

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate that diarrhea-predominant IBS (D-IBS) patients display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose/mannitol method. All subjects ingested 5g of lactulose and 2g of mannitol in 100ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue scale (M-VAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients had increased intestinal membrane permeability as measured by the lactulose/mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8 + or - 5.4) than IBS patients with normal membrane permeability and sensitivity (51.6 + or - 12.7) and controls (6.1 + or - 5.6) (p<0.001). A subset of D-IBS patients had increased intestinal membrane permeability that was associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli.
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PMID:Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. 1959 11

BACKGROUND Linaclotide is a novel, orally administered investigational drug currently in clinical development for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation. Visceral hyperalgesia is a major pathophysiological mechanism in IBS-C. Therefore, we investigated the anti-nociceptive properties of linaclotide in rodent models of inflammatory and non-inflammatory visceral pain and determined whether these pharmacological effects are linked to the activation of guanylate cyclase C (GC-C). METHODS Orally administered linaclotide was evaluated in non-inflammatory acute partial restraint stress (PRS) and acute water avoidance stress (WAS) models in Wistar rats, and in a trinitrobenzene sulfonic acid (TNBS)-induced inflammatory model in Wistar rats and GC-C null mice. KEY RESULTS In TNBS-induced colonic allodynia, linaclotide significantly decreased the number of abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity change in response to distending pressures after TNBS. However, linaclotide had no effect on visceral sensitivity under basal conditions. In addition, linaclotide significantly decreased colonic hypersensitivity in the PRS and WAS models. In wild type (wt) and GC-C null mice, the instillation of TNBS induced similar hyperalgesia and allodynia. However, in post-inflammatory conditions linaclotide significantly reduced hypersensitivity only in wt mice, but not in GC-C null mice. CONCLUSIONS & INFERENCES These findings indicate that linaclotide has potent anti-nociceptive effects in several mechanistically different rodent models of visceral hypersensitivity and that these pharmacological properties of linaclotide are exerted through the activation of the GC-C receptor. Therefore, linaclotide may be capable of decreasing abdominal pain in patients suffering from IBS-C.
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PMID:Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. 1970 70

Gastrointestinal infection is ubiquitous worldwide though the pattern of infection varies widely. Poor hygiene and lack of piped water is associated with a high incidence of childhood infection, both viral and bacterial. However in developed countries bacterial infection is commoner in young adults. Studies of bacterial infections in developed countries suggest 75% of adults fully recover, however around 25% have long lasting changes in bowel habit and a smaller number develop the irritable bowel syndrome (IBS). Whether the incidence is similar in developing countries is unknown. Post-infective IBS (PI-IBS) shares many features with unselected IBS but by having a defined onset allows better definition of risk factors. These are in order of importance: severity of initial illness, smoking, female gender and adverse psychological factors. Symptoms may last many years for reasons which are unclear. They are likely to include genetic factors controlling the immune response, alterations in serotonin signaling, low grade mucosal inflammation maintained by psychological stressors and alterations in gut microbiota. As yet there are no proven specific treatments, though 5HT(3) receptor antagonists, anti-inflammatory agents and probiotics are all logical treatments which should be examined in large well-designed randomised placebo controlled trials.
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PMID:Infection, inflammation, and the irritable bowel syndrome. 1971 78

Stressfull life events have powerful influences on visceral perception of certain IBS patients. In the present study, we aimed to examine the involvement of TRPV1 and TRPA1 in the stress-induced visceral hyperalgesia. Rats were exposed to 1-h water avoidance stress (WAS) daily for 10 consecutive days. The abdominal withdrawal reflex (AWR) to colorectal distension was assessed at the end of the 10-day period. Western-blotting analysis was applied to investigate the alterations of TRPV1 and TRPA1 in the colonic afferent dorsal root ganglia (DRG). Compared with control rats, the WAS-treated rats demonstrated a significant increase in the AWR with the pressure > or = 40 mm Hg (P < 0.05). Meanwhile, in the WAS-treated rats, western-blotting analysis showed significant upregulation of TRPV1 and TRPA1 in the colonic afferent DRG. The results indicate that WAS could induce the upregulation of TRPV1 and TRPA1 in the colonic afferent DRG, and both receptors may be candidate molecules involved in the stress-induced visceral hyperalgesia in rats.
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PMID:Transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) participate in visceral hyperalgesia in chronic water avoidance stress rat model. 2018 91

Mebeverine HCl is a water soluble drug commonly used to treat irritable bowel syndrome by acting directly on the smooth muscles of the colon. This work was aimed at the formulation and in vitro evaluation of a colon-targeted drug delivery system containing mebeverine HCl. Matrix tablets were prepared using ethyl cellulose (EC), Eudragit RL 100 either solely or in combination by wet granulation technique. Dissolution was carried out in 0.1 N HCl for 2?h followed by pH 6.8 phosphate buffer for eight hours. Uncoated forms released more than 5% drug in 0.1 N HCl therefore, Eudragit L100 was used as a coat. The results indicated very slow release profile. As a result, single retardant was used to prepare the matrix and coated by Eudragit L 100. The matrix containing 7% Eudragit RL 100 and 6% of binder was subjected to further studies to assess the effect of different coats (Eudragit L 100-55 and cellulose acetate phthalate) and different binders (pectin and sodium alginate) on the release profile. Eudragit L 100 and pectin were the best coating agent and binder, respectively. The final formula was stable and it can be concluded that the prepared system has the potential to deliver mebeverine HCl in vivo to the colon.
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PMID:Preparation and in vitro evaluation of mebeverine HCl colon-targeted drug delivery system. 2042 15

The authors point out the therapeutic properties of sulphate-bicarbonate mineral waters. After summarizing the general mechanism of action of mineral waters, the main indications of such waters in thermal treatment are examined including: biliary sand, biliary dyskinesia, functional dyspepsia, irritable colon, chronic primitive constipation. The dysfunctions of biliary and digestive tracts are growing, mainly in the affluent world, because of the increase for stress, dietary habits, modern life style. Now they affect from 2,4% of general population to 7% of men and 20% of women, according to different studies. Mineral waters can improve symptoms and care some physiopathological underlying mechanisms. Authors stress the efficacy of sulphate-bicarbonate mineral waters in the therapy of biliary dyskinesias, namely gallbladder hypokinesia and Oddi's sphincter spasm, caused by their content in SO4 = anion and Mg++ cation and related effects on paracrine-endocrine gastrointestinal system. In addition, they report the effects of sulphate-bicarbonate mineral waters in the lithogenic bile (sand bile), because of their diluting and washing activity. Among the sulphate-bicarbonate mineral waters, the Authors outline the well-documented therapeutic activity of Acqua Santa and Fucoli of Chianciano Terme. Acqua Santa has stimulating effect on cholecystis's motility, as proved by controlled clinical trials. Finally, the therapeutic use of sulphate-bicarbonate mineral water is discussed in functional dyspepsia, chronic primitive constipation and irritable bowel syndrome.
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PMID:Sulphate-bicarbonate mineral waters in the treatment of biliary and digestive tract diseases. 2049 33


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