Rectal potential differences in irritable bowel syndrome and in inflammatory bowel diseases in man

We have studied rectal potential difference (pd) in 200 subjects: 30 healthy volunteers or control patients, 46 patients with irritable bowel syndrome (IBS) and painless diarrhoea (group I), 60 IBS patients without diarrhoea (group II) and 64 patients with inflammatory bowel disease (IBD) with (group III, n = 41) or without (group IV, n = 23) rectal involvement. Pd measurement used a rectal perfused probe and a subcutaneous needle both connected, via agar-KCl bridges, to calomel electrodes and a millivoltmeter. Statistical analysis used Student's t-test for paired and unpaired data and Mann-Whitney U-test as appropriate. Mean rectal pd values were, respectively -43.5 +/- 8.7 mV in control group, -32.9 +/- 10.2 mV in IBS-group I patients (P less than 0.001), -41.3 +/- 12 mV in IBS-group II patients (NS), -21.4 +/- 14.1 mV in IBD patients with rectal involvement (P less than 0.001), and -45.1 +/- 14.3 mV in IBD-group IV patients (NS). A histological examination was performed in 36 IBS patients; mean rectal pd was significantly decreased in patients showing abnormal patterns (n = 27, pd = -31.8 +/- 9 mV) compared to patients with normal mucosa (n = 9, pd = -41.1 +/- 6.5 mV; P less than 0.01). These results show that: (1) potential difference is significantly decreased in patients with ulcerative and rectal involvement; (2) in patients with Crohn's disease, normal rectal pd values do not assess the appearance of colonic mucosa above; (3) patients with IBS and diarrhoea also present a significant diminution in mean rectal pd. Although the mechanisms involved remain unclear, rectal pd measurement appears to be an objective test for intestinal mucosae weakness in functional or inflammatory diseases of the large intestine and rectum.     

Visceral hypersensitivity following cold water intake in subjects with irritable bowel syndrome

Background Visceral hypersensitivity has been shown to be present in irritable bowel syndrome (IBS). This study sought to investigate rectal sensitivity and abdominal symptoms in IBS patients before and after 220 ml cold water intake. Methods A total of 60 IBS patients and 18 healthy controls participated in this study. Both the perception thresholds and defecation thresholds to rectal balloon distension were measured. Then, all subjects were asked to drink 220 ml 37°C warm water or 4°C cold water, and these steps were repeated 20 min later. Symptoms including abdominal pain/discomfort, bloating, and diarrhea were recorded during the study. Results Compared with the controls, the thresholds of initial sensation to rectal balloon distention in IBS patients were significantly lower while the defecation thresholds were higher in constipation-predominant IBS patients. After drinking cold water, the perception thresholds in IBS patients and the defecation thresholds in diarrhea-predominant IBS patients were further decreased. However, warm water intake did not change the perception thresholds significantly in either IBS patients or controls. A negative linear correlation was found between the symptoms and the visceral perception thresholds in diarrhea-predominant IBS patients who showed significant symptoms after cold water intake. Conclusion The results indicated that cold water intake leads to lowered visceral perception thresholds in IBS patients that were inversely relevant to the abdominal symptoms in symptomatic diarrhea-predominant IBS patients. The alteration of rectal sensitivity and abdominal symptoms following cold water stimulation provided further objective evidence for visceral hypersensitivity in IBS patients.     

Visceral perception thresholds after rectal thermal and pressure stimuli in irritable bowel syndrome patients

BACKGROUND AND AIM: Visceral hypersensitivity has been shown to be present in irritable bowel syndrome (IBS). The current study sought to compare the characteristics of visceral perception thresholds after rectal thermal and pressure stimuli between IBS patients and healthy subjects. METHODS: A total of 46 patients with IBS were diagnosed using Rome II criteria. Thirteen healthy individuals participated in the study. Rectal visceral perception thresholds were examined in patients with IBS and in normal controls after thermal and pressure stimuli. Subjects were asked to report the sensation type, location, and spread. RESULTS: Compared with healthy subjects, IBS patients demonstrated significantly initially lower perception thresholds and defecation thresholds to rectal thermal and pressure stimuli, particularly in patients with diarrhea-predominant IBS. Ice stimuli on the abdominal wall had varied effects on symptoms in patients with IBS and did not affect perception thresholds. CONCLUSIONS: Visceral perception thresholds were decreased significantly after rectal thermal and pressure stimuli in patients with IBS. Visceral hypersensitivity may be one of the important pathogenic mechanisms in IBS.     

Visceral perception in irritable bowel syndrome

We wished to determine if visceral perception in the rectum and stomach is altered in patients with irritable bowel syndrome and to evaluate the effects on visceral sensation of 5-HT₃ receptor blockade. Twelve community patients with diarrhea-predominant irritable bowel syndrome and 10 healthy controls were studied in a double-blind, randomized, placebo-controlled study. Using two barostats, the stomach and rectum were distended, with pressure increments of 4 mm Hg, from 10 to 26 mm Hg; visceral perception was measured on an ordinal scale of 0–10. Personality traits were measured using standard psychological methods, and somatic pain was evaluated by immersion of the nondominant hand in cold water. The effect of 5-HT₃ antagonism was tested with a single intravenous dose of ondansetron at 0.15 mg/kg. Gastric perception was higher in irritable bowel syndrome, but rectal distension was perceived similarly in irritable bowel syndrome and controls. Pain tolerance to cold water was also similar in irritable bowel syndrome and controls. Ondansetron induced rectal relaxation and increased rectal compliance but did not significantly alter gastric compliance or visceral perception. Psychological test scores were similar in patients and controls. We conclude that in this group of psychologically normal patients with irritable bowel syndrome, who were not chronic health-care seekers, visceral perception was normal. Ondansetron did not alter gut perception in health or in irritable bowel syndrome.This work was supported in part by grants AG09440, DK32121, and RR585 from the National Institutes of Health.     

肠康方对肠易激综合征内脏高敏感模型大鼠的作用

[目的]探讨肠康方对肠易激综合征(IBS)内脏高敏感模型大鼠的作用.[方法]制备肠易激综合征内脏高敏感模型,将72只Sprague-Dawley大鼠随机分为6组,即模型组,空白对照组,阳性药物对照组,肠康方高、中、低剂量组.在造模第60天开始灌胃给药或0.9％氯化钠溶液共10d,干预后通过腹肌回缩反射(AWR)半定量评分测定大鼠内脏敏感性.[结果]不同压力下模型组AWR评分显著高于空白对照组,肠康方高、中、低剂量组治疗后AWR评分均显著低于模型组(P＜0.05或P＜0.01).[结论]肠康方可通过改善内脏高敏感治疗IBS.     

肠易激综合征发病机制研究进展

肠易激综合征（irritable bowel syndrome,IBS）是常见的功能性肠病,以腹痛伴有大便性状和排便习惯改变为主 要表现。IBS 发病机制复杂,包括了增加IBS易感性的因素及与症状发作相关的因素,多种因素相互作用导致了相应 的病理生理变化,从而产生IBS症状,文章就已有的研究结果对IBS的发病机制进行总结。     

Evidence for autonomic dysregulation in the irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and visceral hypersensitivity. In this study, resting blood pressure and heart rate were recorded in 20 IBS patients and 23 controls. We assessed pain intensity and unpleasantness to visceral and cutaneous stimuli using rectal distension and immersion of the foot in hot water. Mean resting heart rate was higher in IBS patients compared to controls. IBS patients rated pain intensity and unpleasantness to visceral and cutaneous stimuli significantly higher than controls. In IBS patients, blood pressure was significantly inversely associated with visceral pain and only weakly and positively associated with cutaneous pain; there were no relationships in controls. Sex and anxiety did not explain these relationships. In conclusion, we found evidence suggestive of central autonomic dysregulation in IBS patients.     

Alterations in cerebral potentials evoked by rectal distention and drinking ice water in patients with irritable bowel syndrome

AIM: Visceral hypersensitivity has been found to be present in irritable bowel syndrome (IBS). The current study sought to study visceral afferent hypersensitivity in IBS patients and obtain further objective evidence of alterations in intestinal afferent pathways in IBS patients by cerebral evoked potentials (CEP). METHOD: We studied 30 female IBS patients and 12 female healthy subjects. Rectal perception thresholds to balloon distention were measured and CEP was recorded in response to rhythmic rectal distention (two distention series, each of 100 repetitions at a frequency of 1 Hz) at the volume of perception thresholds. All subjects were then asked to drink 220 mL 4 degrees C ice water and the above steps were repeated 20 min later. RESULTS: Rectal distention led to recognizable and reproducible CEP. Compared to healthy subjects, IBS patients demonstrated significantly shorter N1, P1 and N2 latencies (P < 0.05). After drinking ice water, IBS patients exhibited further shortened N1, P1 and N2 latencies (P < 0.05), but drinking did not alter the latencies of healthy controls and the amplitudes of both IBS patients and healthy controls. CONCLUSION: The shorter latency of cerebral potentials evoked by rectal distention and ice water stimulation in IBS patients provided further objective evidence for defective visceral afferent transmission in IBS patients.     

Colonoscopy as an adjunctive method for the diagnosis of irritable bowel syndrome: Focus on pain perception

Background and Aim: Visceral hypersensitivity is an important component of the pathophysiology of irritable bowel syndrome (IBS). In the present study, we investigated differences in pain perception during colonoscopy between IBS patients and non‐IBS patients. We further assessed the sensitivity, specificity, and predictive values of pain scores to diagnose IBS. Methods: Patients who underwent colonoscopy for the evaluation of gastrointestinal symptoms or for screening purposes were included. All patients completed Rome III criteria questionnaires and reported pain scores on 0–100‐mm visual analog scales after colonoscopy. The patients were divided into three groups: (i) IBS; (ii) other functional gastrointestinal disorders (FGID), including functional bloating, functional diarrhea, and functional constipation; and (iii) healthy controls. Results: A total of 217 patients were included. The pain scores (median, interquartile range) of IBS patients (52, 34–71) were higher than those of the healthy controls (22, 12–35) or other FGID patients (18, 10–29) (P < 0.001). Upper gastrointestinal symptoms were observed more often in the IBS group than in the non‐IBS group (83.2% vs 34.5%, P < 0.001). At the pain score level of 31, the sensitivity, specificity, positive predictive value, and negative predictive value for IBS diagnosis were 86.1%, 75.9%, 75.7%, and 86.3%, respectively. Conclusions: The degree of pain perception during colonoscopy was higher in IBS patients than in non‐IBS patients. We concluded that colonoscopy can be useful in identifying IBS patients, with the additional benefit of excluding organic disorders of the lower gastrointestinal tract.     

腹部冷刺激对肠易激综合征患者内脏感觉阈值的影响

目的 探讨腹部冷刺激对肠易激综合征（IBS）患者内脏褡珠影响。方法 通过脐部放置冰袋加直肠球囊内充气（时相性）和直肠球囊内注入冰水，观察46例IBS患者症状变化及直肠初始感觉阈值和排便阈值，并与13例健康人对照。结果 （1）脐部放置冰袋加直肠球囊内充气可诱发部分患者症状的产生，如腹痛、腹部不适等，但对初始感觉阈值和排便阈值无明显影响。（2）直肠球囊内注入冰水后，除便秘型IBS的排便阈值稍有所增加但差异不显著外，其余患者初始感觉阈值及排便阈值均明显低于对照组，以腹泻型变化最明显。结论 腹部冷刺激对IBS患者内脏感觉阈值无明显影响，而直肠内冷刺激可明显降低初始感觉阈值，说明IBS患者感觉过敏并非整体痛阈降低所致，而仅指内脏感觉过敏。     

An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome

BACKGROUND/AIMS: Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood. SUBJECTS: We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS. METHODS: Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined. RESULTS: Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group. CONCLUSIONS: Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.     

Mast cells and neuropeptidergic terminals: Experimental studies of the mechanism of visceral hypersensitivity in irritable bowel syndrome

OBJECTIVE: The failure of dysmotility to explain the symptoms of pain in irritable bowel syndrome (IBS) led to studies on visceral hypersensitivity. Mucosal mast cells (MC) may be one factor influencing the response of visceral afferents to mechanical and chemical stimuli because they are found in close proximity to gastrointestinal mucosal sensory nerve terminals containing neuropeptides and a bi‐directional pathway linking the central nervous system, gut and MC has been demonstrated. METHODS: The present study investigated the extent of MC and the neuropeptides, substance P (SP) and vasoactive intestinal peptide (VIP), in the intestinal mucosa of patients with IBS, as well as the location of the MC. The MC and neuropeptidergic terminals were stained histochemically and immunohistochemically, respectively, neuropeptide concentrations were measured by radioimmunoassay (RIA), and the results were investigated qualitatively and quantitatively by color image analyzer. The structural relation between the MC and neuropeptide terminals was studied by ultramicroscopy using in situ embedding technique. RESULTS: In IBS, the number of MC in the terminal ileum, the ileocecal junction, and the ascending colon was significantly increased (P < 0.01), and the MC had great variations in their extent and size. Significantly increased concentrations of VIP and SP were found in the colon of IBS patients compared with controls. A correlation between mucosal MC and the SP(VIP)‐ergic terminals was found, and the MC were close to these terminals in the lamina propria, which demonstrated SP (VIP)‐ergic terminals. CONCLUSIONS: Mast cells and the neuropeptides of intestinal mucosa may play a central role in gut hypersensitivity, resulting in both the motor response and visceral perceptions that occur with IBS.     

肠易激综合征内脏感觉过敏动物模型的建立

目的 内脏感觉过敏是肠易激综合征(IBS)的主要发病机制之一，本文利用大鼠建立一种内脏感觉过敏的动物模型。方法8～21天雌雄Wistar大鼠每天接受不同压力的结肠机械刺激，成年后直肠扩张时记录大鼠腹肌收缩反应(AWR)评分，并进行降结肠的组织学检查。结果 ①新生儿时期接受不同压力结肠机械刺激的大鼠成年后直肠扩张时AWR评分明显高于对照组，不同压力机械刺激组间AWR评分无明显差异，雌性大鼠AWR评分明显高于雄性大鼠。②各组大鼠降结肠常规病理切片未见明显异常。结论 Wistar大鼠在新生儿时期接受的结肠刺激可造成无明显病理改变的慢性内脏感觉过敏模型，雌性大鼠更具有易感性。     

Post-infectious irritable bowel syndrome in patients with Shigella infection

BACKGROUND AND AIMS: Bacterial gastroenteritis has been known as a risk factor of irritable bowel syndrome (IBS). Several risk factors of post-infectious IBS (PI-IBS) have been documented. The aims of this study were to verify the role of bacterial gastroenteritis in the development of IBS and the risk factors for the development of PI-IBS. The clinical course of PI-IBS was also investigated. METHODS: We recruited 143 patients with shigellosis during its outbreak and 113 controls. Both groups were followed up for 12 months. Bowel symptoms were evaluated by use of questionnaires at 3, 6 and 12 months after the initial recruitment. RESULTS: Complete data were obtained from 101 patients (70.6%) and 102 healthy controls (90.3%). At 12 months, 15 patients and six controls had IBS (adjusted OR; 2.9, 95% CI; 1.1-7.9). Of the 15 patients, five had IBS symptoms consistently for 12 months, three did not have IBS symptoms initially and seven had fluctuating bowel symptoms. The duration of diarrhea was an independent risk factor of PI-IBS. CONCLUSIONS: Bacterial gastroenteritis is a risk factor of IBS and the duration of diarrhea as the index of severity of initial illness is an independent risk factor of PI-IBS. The clinical course of PI-IBS is variable over the 1 year of follow-up.     

腹泻型与便秘型肠易激综合征直肠肛管动力和感觉功能的不同特点

目的 研究腹泻型与便秘型肠易激综合征（IBS）病人直肠肛管动力和直肠感觉功能的不同特点。方法 选择IBS病人85例，分成两组。其中腹泻组52例，便秘组33例，20例健康志愿者为对照组，采用PC Polygraf ID高分辨率多道胃肠功能测定仪，分别测定直肠肛管压力、直肠感知阈值、排便阈值、最大耐受量和直肠肛门抑制反射最低充气量。结果IBS病人的直肠静息压、肛管静息压和直肠肛门抑制反射最低充气量与健康对照组比较无显著性差异。腹泻组的最大缩窄压和排便阈值显著低于健康对照组。便秘组的松弛压、直肠感知阈值、排便阈值和最大耐受量显著高于健康对照组。结论腹泻型IBS病人的症状与最大缩窄压和排便闽值降低有关；而便秘型则与松弛压、直肠感知阈值、排便阈值和最大耐受量显著增高有关。     

Sex differences in irritable bowel syndrome in Japanese university students

Background Epidemiological studies of irritable bowel syndrome (IBS) among young adults are few, especially in Asian countries. Our aim was to examine the prevalence of IBS, whether there was a sex difference, and whether allergic diseases were important risk factors for IBS in young adults. Methods Newly enrolled university students completed health survey questionnaires regarding general health. Those with gastrointestinal symptoms completed the Gastrointestinal Symptom Rating Scale (GSRS) and an additional questionnaire covering the presence of allergic manifestations. IBS was diagnosed based on the Rome II criteria. Results IBS was diagnosed in 268 of 2495 students [10.7%; constipation-predominant type (IBS-C), 128; diarrhea-predominant type (IBS-D), 117; unclassified, 23]. IBS-C was associated with female sex (odds ratio, 6.4; 95% confidence interval, 4.1–9.7; P < 0.001), whereas there was no sex difference in IBS-D. The proportions of subjects with food sensitivity were significantly different among the three groups (4.0%, subjects without IBS; 8.6%, IBS-C group; and 15.4%, IBS-D group) (P < 0.001). The median GSRS scores for pain (1.67 vs 1, P = 0.001), indigestion (1.75 vs 1.5, P < 0.001), and constipation (2.0 vs 1.33, P < 0.001) were higher, and the median diarrhea score was lower (1.33 vs 1.67) (P < 0.001), in women than in men. The median score for diarrhea (2.33 vs 1.67, P = 0.001) was significantly higher in subjects with food sensitivity than in those without. Conclusions There was a strong relationship between IBS-C and female sex, and food sensitivity seemed to be an exacerbating factor for IBS-D. There is no conflict of interest.     

Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome

The last ten years’ wide progress in the gut microbiota phylogenetic and functional characterization has been made evidencing dysbiosis in several gastrointestinal diseases including inflammatory bowel diseases and irritable bowel syndrome (IBS). IBS is a functional gut disease with high prevalence and negative impact on patient’s quality of life characterized mainly by visceral pain and/or discomfort, representing a good paradigm of chronic gut hypersensitivity. The IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain. Further, gut microbiota modulation by antibiotics or probiotics has been promising in IBS. Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitization and/or activation.     

Repetitive rectal painful distention induces rectal hypersensitivity in patients with irritable bowel syndrome

Background A reduced rectal perceptual threshold has been reported in patients with irritable bowel syndrome (IBS), but this phenomenon may be induced by a comorbid psychological state. We evaluated the rectal pain threshold at baseline and after conditioning (repetitive rectal painful distention: RRD) in patients with IBS or functional abdominal pain syndrome (FAPS), which is an abdominal pain disorder, and in healthy controls, and determined whether rectal hypersensitivity is a reliable marker for IBS. Methods The rectal sensory threshold was assessed by a barostat. First, a ramp distention of 40 ml/min was induced, and the threshold of pain and the maximum tolerable pressure (mmHg) were measured. Next, RRD (phasic distentions of 60-s duration separated by 30-s intervals) was given with a tracking method until the subjects had complained of pain six times. Finally, ramp distention was induced again, and the same parameters were measured. The normal value was defined by calculating the 95% confidence intervals of controls. Results Five or six of the seven IBS patients showed a reduced rectal pain threshold or maximum tolerable pressure, respectively, at baseline. In all patients with IBS, both thresholds were reduced after RRD load, but they were reduced in none of the patients with FAPS. RRD significantly reduced both thresholds in the IBS group (P < 0.05), but it had no effect in the control or FAPS groups. Conclusions Rectal hypersensitivity induced by RRD may be a reliable marker for IBS. Conditioning-induced visceral hypersensitivity may play a pathophysiologic role in IBS.