Sensitivity In Irritable Bowel Syndrome Research Articles

Exploring vagal neuromodulation: a novel approach to managing pain sensitivity in irritable bowel syndrome

Exploring vagal neuromodulation: a novel approach to managing pain sensitivity in irritable bowel syndrome Irritable bowel syndrome (IBS) is a common, chronic gastrointestinal disorder characterised by recurring abdominal pain and discomfort. This project will work under the hypothesis that IBS is linked to a malfunctioning of the brain-gut communication axis and proposes to address this dysfunction through transcutaneous electrical vagus nerve stimulation. To assist in identifying IBS patients suitable for this treatment, the study team aims to develop a neural signature using biometrics and neuroimaging. The study has the potential to revolutionise the treatment of IBS and other pain disorders, providing personalised and effective therapies.

Self-reported Wheat Sensitivity in Irritable Bowel Syndrome and Healthy Subjects: Prevalence of Celiac Markers and Response to Wheat-free Diet.

Background/AimsMost patients with irritable bowel syndrome (IBS) report food-related aggravation of symptoms. Wheat/gluten is one of the most commonly incriminated. We studied the prevalence of self-reported wheat sensitivity in patients with IBS and in a healthy population from a region in India consuming mixed-cereal diets, correlated it with serological and human leukocyte antigen (HLA) markers of celiac disease, and evaluated the response to a wheat-free diet.MethodsWe surveyed 204 patients with IBS and 400 healthy persons for self-reported wheat sensitivity. Testing for IgA anti-tissue transglutaminase and HLA DQ2 or DQ8 was done in individuals who reported wheat sensitivity. Consenting persons with wheat sensitivity were put on wheat-free diet and monitored for symptom change.ResultsTwenty-three of 204 patients with IBS (11.3%) and none of the healthy subjects self-reported wheat sensitivity. Of 23 patients, 14 (60.9%) were positive for HLA DQ2 or DQ8 and none for anti-tissue transglutaminase antibody. After 6 weeks on wheat-free diet, all 19 participating patients reported clinical improvement; fewer patients had bloating, diarrhea, constipation, and easy fatigue.ConclusionsEleven percent of patients with IBS self-reported wheat sensitivity. None of them had positive celiac serology; 60.9% were positive for HLA DQ2 and DQ8, suggesting a possible genetic basis. All of them improved symptomatically on a wheat-free diet.

The mechanisms of action of WeiChang'An Pill (WCAP) treat diarrhoea-predominant irritable bowel syndrome (IBS-D) using network pharmacology approach and in vivo studies

Ethnopharmacological relevanceWeiChang’An Pill (WCAP) is used in Traditional Chinese Medicine (TCM) to clinically treat diarrhoea-predominant irritable bowel syndrome (IBS-D); however, the underlying pharmacological mechanisms are unclear to date. Aim of the studyTo explore the mechanism underlying the therapeutic action of WCAP in IBS-D using a network pharmacology approach and in vivo experiments. Materials and methodsThe active compounds of WCAP were selected from the TCM Systems Pharmacology Database and TCM Integrated Database, and the potential targets were identified using the Swiss Target Prediction and Similarity Ensemble Approach (SEA) databases. The targets related to IBS-D were mined from the Therapeutic Target Database (TTD), National Center for Biotechnology Information Search database (NCBI), DrugBank database, and DisGeNET database. The intersecting protein-protein interactions (PPIs) of the drug-disease crossover genes were analysed, and the central PPI network was constructed using the String database, version 11.0, and Cytoscape version 3.7.2. Following Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway analyses, the gene-pathway network was constructed for identifying the key target genes and pathways. Based on the results and existing evidence, it was selected the cyclic adenosine monophosphate (cAMP) signalling pathway for further validation using in vivo experiments. ResultsA total of 872 targets were identified from the 77 active compounds in WCAP, which shared 78 targets that were predicted to be related to IBS-D. Twenty-one core targets were identified from the PPI network, which was constructed from the common targets. The results of enrichment analysis revealed that HRT2B, ADRA1A, ADRA1D, and CHRM2 could be the key targets of WCAP in IBS-D, and 11 signalling pathways, including the neuroactive ligand-receptor interaction, calcium signalling, and cAMP signalling pathways, were identified as crucial for the therapeutic activity of WCAP in IBS-D. We also identified the possibility of several interactions and crosstalk between the different pathways. Subsequent molecular biology experiments revealed that the expression levels of cAMP, phospho-(Ser/Thr) protein kinase A substrates (p-PKA), 5-hydroxytryptamine, and proteins in the cAMP signalling pathway, including G protein-coupled receptor (GPCR), adenylyl cyclase 5 (AC5), and cAMP-response element binding protein (CREB), were significantly upregulated in rat models of IBS-D following treatment with WCAP (P < 0.05). However, a reverse trend was observed in the expression of nuclear factor kappa-B (NF-κB) (P < 0.05), which could be attributed to the low-grade inflammation that occurs in IBS-D. ConclusionWe demonstrated that WCAP may alleviate the symptoms of diarrhoea and visceral sensitivity in IBS-D by regulating the cAMP signalling pathway.

MicroRNA-495 reduces visceral sensitivity in mice with diarrhea-predominant irritable bowel syndrome through suppression of the PI3K/AKT signaling pathway via PKIB.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the most common gastrointestinal disorders in the world, lacking effective therapies. The crucial roles of microRNAs (miRNAs) in IBS-D have attracted increasing attention. The aim of this study is to investigate the effects of miR-495 on the visceral sensitivity of the IBS-D through the PI3K/AKT signaling pathway by targeting PKIB. Microarray data analysis was employed to screen the differentially expressed genes related to IBS-D and regulatory miRNAs. Then, mice were perfused with acetic acid into the rectum to establish the IBS-D model. Next, PKIB expression was measured in IBS-D mice. Additionally, model mice were injected with a series of adenovirus vector to investigate the influence of miR-495 on visceral sensitivity and rectal function in IBS-D mice with the involvement of PKIB and PI3K/AKT signaling pathway. The IBS-D mouse model was successfully established. PKIB was the target gene of miR-495, and highly expressed in mice with IBS-D. Silencing PKIB reduced visceral sensitivity in mice with IBS-D, and overexpression of miR-495 decreased visceral sensitivity in mice with IBS-D by inhibiting PKIB. Moreover, miR-495 upregulation inhibited PI3K/AKT signaling pathway through downregulating PKIB. To sum up, this study reveals that miR-495 upregulation can reduce visceral sensitivity in IBS-D via inhibition of PI3K/AKT signaling pathway by targeting PKIB. It suggests that miR-495 presents a potential target for IBS-D therapy.

The relationship between adherens junction and tight junction and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome

Objective: To investigate the association between adherens junction proteins E-cadherin and β-catenin and tight junction protein claudin-2 and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome (IBS-D). Methods: Cecal biopsy tissues were collected from IBS-D patients (n=26) according to Rome Ⅲ criterion and healthy controls (n=26). The duration of symptoms, abdominal pain score and mean weekly bowel movements were recorded. Colorectal dilatation combined with restraint stress were applied to establish visceral hypersensitivity rat model. Abdominal contraction reflex (AWR) was applied to assess the visceral sensitivity in rats. The stool frequency within 1 hour was recorded after establishing the rat model. The expression of E-cadherin、β-catenin and claudin-2 were assessed by Western blot and immunofluorescence microscopy. Intercellular ultrastructure was observed by transmission electron microscopy. Results: Compared with the healthy controls, the protein expression of E-cadherin and β-catenin in cecal epithelium in IBS-D patients were significantly lower (P=0.015 and P=0.005, respectively), while claudin-2 was significantly higher (P=0.000). Reduced E-cadherin and β-catenin expression was associated high abdominal pain score (r=-0.463, P=0.017 and r=-0.407, P=0.039). The lower expression of β-catenin was associated with longer duration of symptoms (r=-0.458, P=0.019). The protein expression of E-cadherin and ß-catenin in the cecal epithelium of the visceral hypersensitivity rats were significantly lower (P=0.004 and P=0.003, respectively), while claudin-2 was significantly higher (P=0.008). Reduced E-cadherin and ß-catenin expression was associated high visceral sensitivity in IBS-D rats (r=-0.639, P=0.047 and r=-0.888, P=0.001). Conclusions: Intercellular ultrastructure alterations well as cecal β-catenin and E-cadherin protein expression decrease and are associated with high abdominal pain score in IBS-D patients and hypersensitivity rats. β-catenin is further associated with prolonged duration of symptoms in IBS-D patients. The expression of E-cadherin and β-catenin may play a vital role in visceral sensitivity and intestinal barrier dysfunction in IBS-D.

Relationships between psychological state, abuse, somatization and visceral pain sensitivity in irritable bowel syndrome.

Psychological states may interfere with visceral sensitivity. Here we investigate associations between psychosocial factors and visceral sensitivity in irritable bowel syndrome (IBS). Two IBS patient cohorts (Cohort 1: n = 231, Rome II; Cohort 2: n = 141, Rome III) underwent rectal barostat testing, and completed questionnaires for anxiety, depression, somatization, and abuse. The associations between questionnaire measures and visceral sensitivity parameters were analyzed in three-step general linear models (step1: demographic and abuse variables; step 2: anxiety and depression; step 3: somatization). Cohort 1. Pain threshold was positively associated with age and female gender, and negatively with adult sexual abuse and somatization. Pain referral area was negatively associated with age and positively with somatization and GI-specific anxiety, the latter effect mediated by somatization. Cohort 2. Pain threshold was positively associated with age and male gender, and negatively with adult sexual abuse. Pain intensity ratings were positively associated with somatization, female gender and depression, the latter effect mediated by somatization. Somatization is associated with most visceral sensitivity parameters, and mediates the effect of some psychological factors on visceral sensitivity. It may reflect a psychobiological sensitization process driving symptom generation in IBS. In addition, abuse history was found to independently affect some visceral sensitivity parameters.

Effect of transcranial magnetic stimulation on rectal sensitivity in irritable bowel syndrome: a randomized, placebo‐controlled pilot study

Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex can induce analgesic effects in patients with chronic pain syndromes through its effect on central pain-modulatory systems. Our aim was to evaluate the effect of rTMS on rectal sensitivity in irritable bowel syndrome (IBS) patients. In this randomized, sham-controlled, proof-of concept trial, 21 IBS patients (11 women and 10 men; mean age 44.0±12.6years) were randomized, using a double-blind crossover protocol, to active or sham rTMS for 5days of treatment. The primary outcome was the increase in the pressure pain threshold after rTMS. Secondary outcomes were the changes in maximum tolerated rectal volume, rectal compliance and average pain intensity between baseline and the end of the treatments. There were no statistically significant differences between active and sham rTMS in terms of an increase in the pressure pain threshold, maximum tolerated volume and rectal compliance at the end of the treatments compared with baseline. However, in the subgroup of patients with the most marked rectal hypersensitivity, the volume threshold was significantly improved by active, but not by sham, rTMS (P=0.03). Patients experienced a significant improvement in pain regardless of the type of stimulation. This pilot study failed to demonstrate any benefit of rTMS on our primary end-point. However, the effect of rTMS on rectal tolerated volume in the most hypersensitive patients was encouraging enough to plan more powered studies.

Are Bloating and Abdominal Distention Attributed to Gas Production and Visceral Sensitivity in Irritable Bowel Syndrome? (Am J Gastroenterol 2013;108:1516-1525)

Bloating and abdominal distension are common symptoms in patients with irritable bowel syndrome (IBS). Bloating is considered as a subjective sensation and abdominal distention as an objective sign, i.e., the visible increase in abdominal girth.1,2 They can be related to each other or not. Recently, Zhu et al3 evaluated the effects of dietary factors on abdominal bloating and distention and the underlying pathophysiology in IBS. More specifically, they assessed the effects of gas production and visceral hypersensitivity on gastrointestinal (GI) symptoms after lactose ingestion in a population with lactase deficiency. IBS patients (n = 277) and healthy controls (HCs, n = 64) underwent a 20 g lactose hydrogen breath test (LHBT) for evaluation of hydrogen gas production and lactose intolerance (LI) symptoms. Cumulative breath hydrogen excretion was quantified by measuring areas under the curve during LHBT. Five digestive symptoms characteristic of LI (bloating, borborygmi, nausea, pain and diarrhea) were recorded at 15-minute intervals on a scale of 0-4 for 3 hours. Subjects who reported more than one point rise in LI symptoms during the LHBT were diagnosed as LI. Abdominal girth (199 IBS, 40 HCs) was measured in the standing and supine position, before and after LHBT, to evaluate the abdominal distension, using an inextensible metric tape measure over the umbilicus. Abdominal distention was defined to be increased by a minimum distention level of ≥ 0.5 cm. Rectal sensitivity (74 IBS, 64 HCs) was assessed by barostat studies and visceral hypersensitivity was defined as below the 5.0 percentile limit for sensory threshold to discomfort/pain obtained from HCs. In the results, cumulative hydrogen excretion (AUC) during LHBT showed no difference between the groups (P = 0.485) and the prevalence of abdominal distention after lactose ingestion (standing: 58% vs. 72.5%, P = 0.083; supine: 65% vs. 75%, P = 0.213) was similar. In contrast, LI was more frequent in IBS (53.8 vs. 28.1%, P < 0.001), especially bloating (39.0 vs. 14.1%, P < 0.001) and borborygmi (39.0 vs. 21.9 %, P = 0.010). Only 59.0% of patients with bloating had distention. Hydrogen production as well as bloating score was not associated with girth increment. In the multivariate analysis for the factors associated with LI symptom severity, hydrogen production increased bloating (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.09-4.39; P = 0.028) and borborygmi (OR, 12.37; 95% CI, 3.34-45.83; P < 0.001) but not distention (P = 0.673). Visceral hypersensitivity was associated with bloating (OR, 6.61; 95% CI, 1.75-25.00; P = 0.005) and total symptom score (OR, 3.78; 95% CI, 1.30-10.99; P = 0.014). The authors concluded that hydrogen gas production and visceral hypersensitivity both contribute to bloating and borborygmi, in IBS patients after lactose ingestion. Objective abdominal distention is not correlated with subjective bloating as well as gas production.

Tu2058 The Combined Nutrient and Lactulose Challenge Test: A New Non-Invasive Test for Visceral Sensitivity in Irritable Bowel Syndrome (IBS)

Background: Idiopathic bile acid malabsorption (BAM) causes chronic diarrhea and BA deficiency may cause constipation. BA supplementation and an ileal BA transporter inhibitor, elobixibat, accelerate colonic transit (CT). Rectal infusion of BA (e.g. chenodeoxycholate) induces colonic propulsive motility. Up to 50% of patients with IBS-D have accelerated CT; 20% of patients with IBS-C have delayed CT. The relationship between fecal BA excretion, CT, and bowel symptoms in IBS is unclear and may be relevant to selecting optimal therapy. Aim: To assess stool frequency (number) and consistency (form) in relation to CT and fecal BA excretion in healthy participants and patients with IBS-C and IBS-D. Methods: In a prospective study of 92 participants (31 healthy, 30 IBS-C and 31 IBS-D by Rome III criteria), we measured total and individual fecal BA and fecal fat (on 100g fat diet), overall CT by validated scintigraphy (geometric center, GC at 24 and 48h) and stool characteristics by a 14 day bowel pattern diary including Bristol stool form scale. Univariate associations between endpoints were assessed using Spearman correlation (rs). Relationships between stool characteristics, CT and fecal BA excretion were assessed using response surface multiple regression models (which included BMI as a covariate and linear, quadratic and cross product terms for the CT and BA measurements). Results: 1. There were significant univariate associations (table showing rs) between stool number and stool form and total fecal BA (including % LCA, % CDCA, and % CA), fecal fat, and GC24 and 48. 2. The response surface model for stool number (figure left panel) with total fecal BA and CT (GC24 ) explained 29% of the variation (r=0.54, p,0.001); similarly, the model for stool form (figure middle panel) with fecal BA and CT (GC24) explained 20% of the variation (r=0.45, p=0.021). Using total secretory BA (CA+DCA+CDCA), the response surface model for stool form (figure right panel) explained 23% of the variation (r=0.49, p=0.006). In these models, the relative contribution of CT was consistently greater than that for BA, with the coefficients corresponding to CT being statistically significant (p,0.05), while those for BA were borderline (e.g. p=0.073 for the coefficient for secretory BA and stool form, and p=0.227 for stool number). Conclusion: Relative to fecal BA, colonic transit is the greater determinant of stool number and stool form; increased total and secretory fecal BA enhance the effects of colon transit on stool characteristics, but are not independently significant factors. Funding:NIHDK92179

A Combined Nutrient and Lactulose Challenge Test Allows Symptom-Based Clustering of Patients With Irritable Bowel Syndrome

The aim of the present pilot study was to evaluate the usefulness of a test meal containing lactulose in the non-invasive assessment of visceral sensitivity in irritable bowel syndrome (IBS), and to identify subsets of IBS patients based on gastrointestinal (GI) symptom generation. We included 43 patients with IBS (Rome III) and 29 healthy controls. The fasted subjects were served three test meals consisting of a 400-ml liquid breakfast alone or containing lactulose (15 or 25 g) in a double-blind crossover design. Seven GI symptoms, overall digestive comfort, and exhaled H2/CH4 were assessed at baseline and every 15 min during 4 h after meal intake. Anxiety and depression were assessed only at baseline. A mapping of the seven GI symptoms was done using a Principal Component Analysis (4 h mean area under the curve, AUC). Independently, a hierarchical cluster analysis was performed on the same parameters to identify GI symptom-based IBS clusters. All three tests were well tolerated. The 25 g lactulose challenge enabled discrimination of IBS from healthy controls according to the symptom response. This challenge also enabled clustering of IBS subjects in two subgroups based mainly on bloating, distension, and discomfort symptoms (2,457 (2,043-2,872), 2,450 (1,910-2,990), 2,602 (2,126-3,079) vs. 537 (383-691), 619 (458-780), 643 (432-854); 4 h mean AUC; P<0.0001), overall digestive comfort (1807 (1318-2295) vs. 3350 (2942-3758); 4 h mean AUC; P<0.0001), and anxiety at baseline (9.2 (7.0-11.5) vs. 5.5 (4.2-6.9); Hospital Anxiety and Depression scale anxiety mean scores; P=0.003). This clustering was independent of the Rome III subtype and the amount of exhaled H2/CH4. The lactulose challenge test seems to be a promising tool to assess visceral sensitivity in IBS, and to subgroup IBS patients based on their symptom pattern.

A comparison between two different in vitro basophil activation tests for gluten- and cow’s milk protein sensitivity in irritable bowel syndrome (IBS)-like patients

The diagnosis of food hypersensitivity (FH) in adult patients with gastrointestinal symptoms, beyond the immediate IgE-mediated clinical manifestations, is very often difficult. The aims of our study were to: 1) evaluate the frequency of FH in patients with irritable bowel syndrome (IBS)-like clinical presentation; and 2) compare the diagnostic accuracy of two different methods of in vitro basophil activation tests. Three hundred and five patients (235 females, age range 18-66 years) were included and underwent a diagnostic elimination diet and successive double-blind placebo-controlled (DBPC) challenges. Two different methods of in vitro basophil activation tests (BAT) (CD63 expression after in vitro wheat or cow's milk proteins stimulation) were evaluated: one was performed on separated leukocytes, and the other on whole blood. Ninety patients of the 305 studied (29.5%) were positive to the challenges and were diagnosed as suffering from FH. BAT on separate leukocytes showed a sensitivity of 86% and a specificity of 91% in FH diagnosis. BAT on whole blood showed a sensitivity of 15%-20% and a specificity of 73% in FH diagnosis (p<0.0001 compared to the other method). About one third of the IBS patients included in the study were suffering from FH and were cured on the elimination diet. The BAT based on CD63 detection on whole blood samples did not work in FH diagnosis and showed a significantly lower sensitivity, specificity and diagnostic accuracy than the assay based on separated leukocytes.

The effects of sildenafil on rectal sensitivity and tone in patients with the irritable bowel syndrome

Visceral tone supposedly affects gut sensitivity in irritable bowel syndrome (IBS). Sildenafil increases nitric oxide and influences visceral compliance. To evaluate the effects of sildenafil tone inhibition on rectal sensitivity. Eight controls and 21 IBS patients (Rome II) were enrolled in a double-blind study, after dosing with placebo or sildenafil (50 mg p.o.). Thresholds for first sensation, first desire to defecate, pain and supraliminar pain were the sensory endpoints, measured with a barostat and 600-mL rectal bag. Pain (100-mm VAS) and depression-anxiety (Hamilton questionnaire) were scored. Irritable bowel syndrome rectal compliance and sensory-endpoint thresholds were similar to controls. Five IBS patients had pain threshold lower than controls 95% confidence interval (hypersensitive). Depression score was greater in IBS than controls (11.9 ± 1.3 vs. 6.3 ± 2.5, P = 0.036). In IBS, pain intensity was nonsignificantly higher (37.6 ± 5.3 mm vs. 23.4 ± 8.5 mm, P = 0.064) and supraliminar pain intensity was greater (45.6 ± 5.4 mm vs. 25.9 ± 5.1 mm, P = 0.044) than controls. IBS rectal relaxation increased volume (155.4 ± 41.3 mL vs. 118.8 ± 47.7 mL, P = 0.004) and tension (193.1 ± 118.6 mmHg mL(-1) vs. 133.2 ± 98.1 mmHg mL(-1) , P = 0.019) for triggering first desire to defecate but not for other perceptions. Sildenafil increased volume for both first desire to defecate and pain in the hypersensitive IBS patients. Sildenafil increased rectal compliance only in diarrhoea-IBS. Mixed-IBS obtained higher anxiety (12.9 ± 1.3 vs. 5.9 ± 3.1, P < 0.05) and depression scores (13.9 ± 1.9 vs. 6.3 ± 2.5, P < 0.05) and reported more intense supraliminar pain (53.6 ± 9.8 mm vs. 25.9 ± 5.1 mm, P < 0.05) than controls. Rectal relaxation following dosing with sildenafil 50 mg increased the first desire to defecate threshold in IBS as a whole, but decreased pain only in the hypersensitive subset. Mixed-IBS presented higher supraliminar pain and anxiety-depression scores.

Serotonin receptor 3A polymorphism c.-42C &gt; T is associated with severe dyspepsia

BackgroundThe association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HT3 receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT), which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity.MethodsData from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial) were analysed. Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR). Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe). Sum score ≥20 was defined severe dyspepsia.ResultsHTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20). This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39) and patients homozygous for the long (L) variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94). Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90).ConclusionsThe HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among patients carrying the 5-HTTLPR L allele suggests an additive effect of the two polymorphisms. These results support the hypothesis that diminished 5-HT3 mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the HTR3A c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.

Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity

Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity

The growing case for an immunological component to irritable bowel syndrome

It is now generally accepted that irritable bowel syndrome (IBS) is a multifactorial condition with a variety of mechanisms being involved in its pathogenesis. In addition to psychological influences, which have probably been somewhat over-rated in the past, abnormalities of motility, visceral sensation as well as the central processing of noxious stimuli have been demonstrated [1]. The condition undoubtedly runs in families suggesting a genetic component and there is increasing evidence for the presence of low-grade inflammation in the gastrointestinal mucosa of at least a proportion of individuals. Dietary factors are also important and it is common for patients to complain that their symptoms are particularly troublesome following a meal. As a consequence they frequently conclude that they must have some form of dietary allergy, they certainly want to discuss the role of food in their condition and usually ask for a diet sheet. In addition, patients are now often seeking, finding and spending a lot of money on commercially available allergy tests of extremely questionable validity.

Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity

Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity

Nutrient‐dependent enhancement of rectal sensitivity in irritable bowel syndrome (IBS)

Food-related gastrointestinal symptoms are common in irritable bowel syndrome (IBS), but the mechanisms behind this are unclear. Enhanced colorectal sensitivity after duodenal lipid administration in IBS patients has been demonstrated. However, the effects of a regular meal on colorectal sensitivity in these patients and the importance of the composition of the meal are not known. On two separate days, 10 IBS patients and 11 controls randomly received a liquid meal (800 kcal), containing 60% calories from fat (fatty meal) or carbohydrate (carbohydrate meal). Using a barostat rectal sensitivity was assessed during four separate distension sequences before, immediately after and 30 and 60 min after the meal. In the patients, the discomfort (P = 0.04) and the pain thresholds (P = 0.007) were gradually reduced after the fatty meal, whereas only a tendency in the same direction was seen after the carbohydrate meal. In patients VAS ratings for pain increased after the fatty meal (P = 0.03), but not after carbohydrates. In the controls, sensory thresholds were not affected by the meals. In IBS, a liquid meal enhances rectal sensitivity, and this seems to be partly nutrient dependent as a fatty meal has more pronounced effects than a carbohydrate meal. This might be of relevance for their postprandial symptoms.

Viscerosensory-cardiovascular reflexes: altered baroreflex sensitivity in irritable bowel syndrome

Animal studies have demonstrated that visceral afferent stimulation alters autonomic cardiovascular reflexes. This mechanism might play an important role in the pathophysiology of conditions associated with visceral hypersensitivity, such as irritable bowel syndrome (IBS). As such, studies in humans are lacking, we measured viscerosensory-cardiovascular reflex interactions in IBS patients and healthy controls. Systolic blood pressure (SBP), heart rate (HR), and arterial baroreflex sensitivity (BRS) were studied in 87 IBS patients and 36 healthy controls under baseline conditions and during mild (15 mmHg) and intense (35 mmHg) visceral stimulation by rectal balloon distension. BRS was computed from continuous ECG and arterial blood pressure signals (Finapres-method) during 5-min periods of 15-min metronome respiration. Baseline SBP and HR were not different between patients and controls. In both groups, SBP increased similarly during rectal stimulation, whereas HR decreased during mild and increased intense stimulation. BRS was significantly higher in patients compared with controls at baseline (7.9 +/- 5.4 vs. 5.7 +/- 3.7 ms/mmHg, P = 0.03) and increased significantly in both groups during mild stimulation. This increase persisted in controls during intense stimulation, but BRS returned to baseline in patients. BRS was not significantly different between groups during rectal distension. This study demonstrates the presence of a viscerosensory-cardiovascular reflex in healthy individuals and in IBS patients. The increased BRS in IBS patients at baseline may either be a training-effect (frequent challenging of the reflex) or reflects altered viscerosensory processing at the nucleus tractus solitarii.

Nutrient-dependent enhancement of rectal sensitivity in irritable bowel syndrome

Nutrient-dependent enhancement of rectal sensitivity in irritable bowel syndrome

Visceral sensitivity in irritable bowel syndrome (IBS) patients with or without fibromyalgia (FMS)

Visceral sensitivity in irritable bowel syndrome (IBS) patients with or without fibromyalgia (FMS)