Rectal hypersensitivity in the irritable bowel syndrome

Studies of rectal sensory thresholds and compliance in patients with the irritable bowel syndrome have produced conflicting results though there is persistent evidence of rectal hypersensitivity particularly in those with diarrhoea-predominant symptoms. This study examined rectal sensation and compliance in 31 patients with constipation-predominant irritable bowel syndrome (mean age 41 years, 27 female) and 17 healthy volunteers (mean age 45 years, 17 female). A rectal balloon was inflated with fluid at a constant rate and the volume and intrarectal pressure at sensory thresholds was recorded. The volumes at first (129 ± 8 vs 229 ± 24 ml, P < 0.001 Mann-Whitney-U test), constant (159 ± 12 vs 286 ± 21, P < 0.001) and maximum tolerated sensation (290 ± 13 vs 509 ± 19, P < 0.001) were all significantly less in the irritable bowel group. There was no significant difference in intrarectal pressures at any of these volumes (29.0 ± 2.2 cmH₂O vs 29.0 ± 2.5, 35.0 ± 2.5 vs 34.0 ± 2.8, 71 ± 2.5 vs 65.0 ± 3.0 respectively). Rectal compliance was significantly less in the irritable bowel group (3.6 ± 0.2 ml/cmH₂O vs 8.7 ± 0.4, P < 0.001). Twenty two patients complained of abdominal pain on balloon inflation, mimicking that experienced as part of their symptoms. Patients with constipation-predominant irritable bowel syndrome have rectal hypersensitivity and reduced compliance.

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Résumé. Des études sue le seuil de sensibilité rectale et de compliance rectale chez des patients porteurs d'un c?lon irritable ont donné lieu à des résultats contradictoires alors même qu'il persiste de manière évidente une hypersensibilité rectale, en particulier chez des patients présentant des diarrhées comme sympt?me prédominant. Cette étude examine la sensibilité rectale et la compliance chez 31 patients dont le c?lon irritable se manifeste de manière prédominante par une constipation (age moyen: 41 ans, 27 femmes) et chez 17 volontaires sains (age moyen: 45 ans, 17 femmes). Un ballon intra-rectal est distendu avec un liquide à vitesse constante et on enregistre le volume et la pression intra-rectale pour des seuils de sensibilité déterminés. Les volumes de perception initiale (129 + 8 vs 229 + 24 ml P < 0.001 au test Mann-Whitney-U), les volumes pour une perception constante (150 + 12 vs 286 + 21, P < 0.001) et les volumes pour des seuils de tolérance maximale (290 + 13 vs 509 + 19, P < 0.001) sont significativement abaissés dans le groupe des c?lons irritables. Il n'y a pas de différence significative dans la pression intra-rectale à aucun des volumes donnés (29,0 + 2,2 cm H₂O vs 29,0 + 2,5, 35,0 + 2,5 vs 34,0 + 2,8, 71 + 2,5 vs 65,0 + 3,0 respectivement). La compliance rectale est nettement abaissée dans le groupe de c?lon irritable (3,6 + 0,2 ml/cm H₂O vs 8,7 + 0,4, P < 0,001). Vingt-deux patients se plaignent de douleurs abdominales lors de la distension du ballonnet semblable à la douleur constitutive d'une partie de leurs sympt?mes. Les patients présentant de manière prédominante une constipation en liaison avec leur c?lon irritable ont une hypersensibilité rectale et une diminution de la compliance rectale.

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Accepted: 17 December 1996     

功能性便秘和便秘型肠易激综合征相关生活因素上的差异

目的比较功能性便秘（FC）与便秘型 IBS 患者相关生活因素的差异。方法纳入2011年2月至2014年12月的255例慢性便秘患者,其中 FC 170例,便秘型 IBS 85例。另纳入同期1年内无消化道症状的170名健康者作为对照组。收集所有纳入者的人口学基本资料、生活习惯资料等。先行单因素分析,将差异有统计学意义的变量纳入多因素 Logistic 回归分析。再将 FC 和便秘型 IBS 的各因素纳入决策树模型,分析不同分类下影响因素的作用。结果单因素分析显示,FC 组与便秘型 IBS 组各生活因素比较差异均无统计学意义（P 均＞0．05）。多因素 Logistic 回归分析显示,与 FC 组比较,便秘型 IBS 组未发现独立保护或危险因素。经过决策树模型分析,最终纳入 BMI、每日饮水量和便秘家族史3个变量,当 BMI＜23．56 kg／m2（除外18．74～＜19．83 kg／m2）时,患 FC 的概率高（最高达79．75％）;当BMI 为18．74～＜19．83 kg／m2,每日饮水量少（＜1 L）时,患 FC 的概率高（66．67％）;当 BMI≥23．56 kg／m2,有便秘家族史时,患便秘型 IBS 的概率最高（70．00％）。该模型的整体预测准确率为64．6％（42／65）, AUC 值为0．688。结论FC 和便秘型 IBS 的发生与多种生活因素密切相关,BMI 低和每日饮水量少是FC 的影响因素,BMI 较高和有便秘家族史是便秘型 IBS 的影响因素。     

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.     

便秘型肠易激综合征患者肛门直肠运动感觉功能及自主神经活性的变化

目的 研究便秘型肠易激综合征(C-IBS)患者肛门直肠感觉运动功能及自主神经活性变化,以探讨C-IBS的发病机制.方法 用电子气压泵及液流灌注压力监测系统对28例C-IBS患者和15名对照组进行肛门直肠测压检查.对其中12例C-IBS患者和8例健康志愿者,通过HRV频域分析比较两组交感神经张力的变化.结果 C-IBS患者的肛门内括约肌最大收缩压、最小抑制容量、直肠顺应性、初始感觉阈值、初次排便阈值、排便窘迫阈值、最大容量感觉阈值均明显低于对照组(P＜0.05).在C-IBS患者组及对照组中,P1/(P1 P2)在产生便意、排便窘迫、最大耐受时均显著高于基础静息状态(P＜0.05);C-IBS患者组P1/(P1 P2)在基础静息、产生初始感觉、产生便意、排便窘迫时显著高于对照组(P＜0.05).结论 C-IBS患者存在直肠感觉过敏和自主神经功能异常,直肠顺应性也显著低于对照组,可能是C-IBS的发病机制之一.     

Visceral hypersensitivity in irritable bowel syndrome

Altered central processing, abnormal gastrointestinal motility and visceral hypersensitivity may be possible major pathophysiology of irritable bowel syndrome (IBS). These factors affect each other and are probably associated with development of IBS symptoms. It has been confirmed that lower pain threshold to colonic distention was observed in most of patients with IBS than healthy subjects. We have investigated pain perception of the descending colon among different subtypes of IBS. There was no difference in pain threshold to colonic distention between IBS with diarrhea and constipation. Some brain regions such as the anterior cingulate cortex (ACC) may play a major role for generating pain and/or pain-related emotion in humans. IBS patients showed greater activation in the perigenual ACC during painful rectal distention compared with healthy subjects. Inflammation, stress and the combination of both stimuli can induce significant increase in visceral sensitivity in animal models. Serotonin (5-HT) can modulate visceral perception. It has been thought that 5-HT(3) receptors may play an important role for conveying visceral sensation from the gut. Corticotropin-releasing hormone (CRH) may also modulate visceral pain hypersensitivity in IBS. CRH receptor-1 antagonist significantly prevented an increase in gut sensitivity in rats. It has been demonstrated that non-specific CRH receptor antagonist α-helical CRH significantly reduced abdominal pain score during gut stimulus in patients with IBS. In conclusion, visceral hypersensitivity is common in IBS patients and probably plays a major role in development of the symptoms and both central and peripheral factors may enhance the pain sensitivity.     

肠易激综合征感觉异常研究进展

肠易激综合征(IBS)是以腹痛和/或腹部不适伴排便异常为特征性症状的一组肠功能障碍性综合征,近年来的研究表明患者结肠对机械、化学、温度、电刺激等感觉过敏,可能是IBS最重要的致病因素之一.此文综述近年来有关肠易激综合征患者肠神经系统、脊髓及中枢神经系统存在结构或功能的异常.     

Tegaserod for the treatment of constipation-predominant irritable bowel syndrome

Tegaserod, a potent, partial serotonin 4 receptor (5-HT4) agonist, is an effective agent for the treatment of females with constipation-predominant irritable bowel syndrome. Tegaserod enhances gastric motility, stimulates peristaltic reflux and intestinal secretion, inhibits visceral sensitivity, and/or shortens colonic transit time. This agent may help women who have failed to respond to diet and exercise, laxatives, and other forms of therapy. The optimal dose of tegaserod is 6 mg twice daily and results in decreased number of days per month with pain, bloating, and days without bowel movements. Tegaserod is less effective in males than females in the treatment of constipation-predominant irritable bowel syndrome. Tegaserod is well tolerated. Diarrhea is the most frequent adverse effect. The diarrhea tends to occur most frequently during the first few months of therapy and decreases with continued administration.     

Rectal function and bowel habit in irritable bowel syndrome

OBJECTIVES: Rectal compliance may influence rectal perception, but their functional implications remain incompletely understood. Our aim was to determine whether rectal function is related to bowel habit in the irritable bowel syndrome. METHODS: The responses to fixed tension rectal distension applied by means of a tensostat were compared among constipation-predominant (n = 9), diarrhea-predominant (n = 7), alternating habit (n = 11) irritable syndrome subgroups, and healthy controls (n = 15). RESULTS: Overall, patients had normal rectal compliance and increased perception, but compliance was lower in diarrhea-predominant as compared to constipation-predominant patients (6.7 +/- 0.7 ml/mmHg vs. 9.9 +/- 0.7 ml/mmHg, respectively; p < 0.05) and perception was higher (39 +/- 6 g vs. 64 +/- 9 g tolerance, respectively; p < 0.05). CONCLUSION: Distinctive tensosensitivity and compliance characterize rectal function in irritable bowel syndrome subgroups with different bowel habit.     

Differentiating functional constipation from constipation-predominant irritable bowel syndrome: management implications

Symptoms of constipation are commonly seen in medical practice. Once other medical causes have been excluded, distinguishing patients who have constipation-predominant irritable bowel syndrome (IBS) from those with functional constipation has been considered useful in terms of planning management. However, the criteria used to distinguish IBS from functional constipation are arguably arbitrary, and the availability of new therapeutic approaches may render such distinctions of little practical relevance. In this article, the author presents a review of the management implications of differentiating constipation-predominant IBS from functional constipation.     

Colonic hypersensitivity is a major determinant of the efficacy of bloating treatment in constipation-predominant irritable bowel syndrome

The pathophysiology of bloating is largely unknown, and many mechanisms have been proposed. An alteration of intestinal gas production may have a role in a subgroup of patients, but available data are conflicting. We have previously shown that hypersensitivity to colonic fermentation is associated with severe bloating in a subgroup of patients with low intestinal gas production. Accordingly, we evaluated whether modification of intestinal gas production improves bloating severity according to the presence of visceral hypersensitivity to colonic fermentation. Twenty-four IBS-C patients with severe bloating underwent intestinal gas production measurement by hydrogen breath test after lactulose, and a recto-sigmoid barostat test in order to evaluate sensitivity thresholds in a basal condition and after induction of colonic fermentation. The subjects were then randomly assigned to receive either rifaximin or placebo according to a double-blind, randomized, cross-over trial. Rifaximin induced an improvement of symptom severity. A post hoc analysis according to the presence of hypersensitivity to colonic fermentation shows that rifaximin induces a significant improvement in symptom severity only in normosensitive, hyperproducer patients. Modulation of colonic flora, in order to reduce fermentation, does not interfere with bloating severity in patients with visceral hypersensitivity, thus suggesting that in this subgroup of subjects gas production is not crucial for the onset of bloating.     

Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome

BACKGROUND & AIMS: This study evaluated the effects of a partial 5-hydroxytryptamine (5-HT)(4) agonist, tegaserod, on gastric small bowel and colonic transit in constipation-predominant irritable bowel syndrome (IBS). METHODS: After a 1 week run-in period, 24 patients with constipation-predominant IBS were randomized to 1 week of tegaserod, 2 mg twice daily, or placebo treatment. Scintigraphic gastric emptying, small bowel transit, and colonic transit were determined before administration of study drug and after 1 week on the medication. Colonic transit was also measured using radiopaque markers and a single radiograph on day 5. RESULTS: Gastric emptying was unaltered by tegaserod. Proximal colonic filling at 6 hours, a measure of orocecal transit, was accelerated by tegaserod (70.4% +/- 1.3% [mean +/- SEM] vs. placebo, 46.4 +/- 1.9; P = 0.015). Proximal colonic emptying half-time and geometric center at 48 hours were also accelerated by tegaserod compared with baseline, but not compared with placebo. Mean colonic transit time was similar in both groups at baseline and after drug administration (tegaserod, 59.5 +/- 2.1 hours; placebo, 62.1 +/- 2.1 hours). CONCLUSIONS: Tegaserod accelerates orocecal transit, tends to accelerate colonic transit, and deserves further study in patients with constipation-predominant IBS.     

便秘型肠易激综合征肛门直肠动力学的临床研究

目的　观察便秘型肠易激综合征 (IBS)的肛门直肠动力学改变。方法　采用灌注式测压装置测定 18例便秘型IBS患者和 15例健康人的肛门直肠压力、直肠对容量刺激的最低敏感量、最大耐受量及直肠顺应性。结果　便秘型IBS的直肠、肛门内外括约肌静息压力、内括约肌主动收缩压、模拟排便时直肠收缩压、内外括约肌净减压与对照组相比无显著性差异。肛门 直肠屏障压便秘型IBS组高于对照组 (P <0 0 5 )。直肠对容量刺激的最低敏感量便秘型IBS组低于对照组 (P <0 0 5 ) ,最大耐受量及顺应性均高于对照组 (P <0 0 1)。结论　便秘型IBS存在肛门直肠动力学异常 ,这种异常可能是导致便秘的原因     

Prevalence of rectal hypersensitivity in patients with irritable bowel syndrome and its clinical subgroups.

AIM: To evaluate the prevalence of rectal hypersensitivity in our irritable bowel syndrome (IBS) patients, the relationship of hypersensitivity to rectal distensibility and the differences in sensitivity among clinical subgroups of IBS. MATERIAL AND METHODS: 18 healthy subjects and 56 IBS patients (Rome-II criteria; 22 diarrhea-predominant, 15 constipation-predominant and 19 alternating). Rectal sensitivity and distensibility were studied by isobaric phasic distension of a poliethilene bag with a barostat. RESULTS: IBS patients showed a lower threshold for discomfort, pain and maximum tolerate distension, without any differences in rectal distensibility. 64% of IBS patients were hypersensitive. 89% of patients with alternating IBS were hypersensitive while only 68% and 26% of patients with diarrhea-predominant IBS and constipation-predominant IBS, respectively, were. There were no differences in rectal distensibility between hypersensitive and normosensitive patients. CONCLUSION: 64% of our IBS patients show rectal hypersensitivity, apparently not related to rectal distensibility. Hypersensitivity is mostly found in alternating IBS patients, and rare in constipation-predominant IBS.     

Effect of a calcium channel blocker and antispasmodic in diarrhoea-predominant irritable bowel syndrome

BACKGROUND: Irritable bowel syndrome (IBS) is a colonic function disorder. Both pinaverlum bromide (a selective calcium channel blocker) and mebeverine (an antispasmodic) are reported to be effective in the long-term (12-16 weeks) treatment of IBS patients. Their efficacy in the short-term treatment of IBS patients and colonic transit time is unclear. Furthermore, substance P and neuropeptide Y have either excitatory or inhibitory effects on colonic motility. Whether the efficacy of both drugs is mediated through these neuropeptides remains unknown. METHODS AND RESULTS: A clinical trial was conducted with 91 patients with diarrhoea-predominant IBS. After basal measurement of the total colonic transit time, IBS patients were randomized to receive either pinaverlum bromide (50 mg, t.i.d.) or mebeverine (100 mg, t.i.d.) for 2 weeks. The symptomatic scores regarding defaecation, total colonic transit time and serum levels of substance P and neuropeptide Y were measured before and after treatments. The daily defaecation frequency was markedly decreased after treatment (pinaverlum bromide, 2.9+/-1.2 vs 2.0+/-1.0, P< 0.05; mebeverine, 2.7+/-1.1 vs 2.1+/-1.0, P< 0.05). The stool consistency became well formed after both treatments (P< 0.05). Both drugs similarly improved the global well-being in these IBS patients (pinaverlum bromide vs mebeverine 73.4 vs 71.8%, P> 0.05). The total colonic transit time was significantly prolonged only after pinaverlum bromide treatment (21.4+/-15.5 vs 30.8+/-14.8 h, P< 0.01). Neither substance P nor neuropeptide Y serum level was significantly changed after either treatments. CONCLUSION: Pinaverlum bromide and mebeverine have similar therapeutic efficacies on diarrhoea-predominant IBS patients. Prolonged colonic transit time may be one of the factors responsible for the efficacy of pinaverlum bromide on the IBS patients. Substance P and neuropeptideY appear less important in the pathogenesis of diarrhoea-predominant IBS.     

Effect of renzapride on transit in constipation-predominant irritable bowel syndrome.

BACKGROUND & AIMS: The aim of this study was to evaluate the dose-ranging pharmacodynamic effects of renzapride, a 5-hydroxytryptamine 4 (5-HT4) receptor full agonist/5-HT3 receptor antagonist, on gastrointestinal transit and symptoms in patients with constipation-predominant irritable bowel syndrome (C-IBS). METHODS: Forty-eight patients (46 women) with C-IBS underwent recording of baseline symptoms for 1 week. Twelve patients per group were randomized (double-blind, parallel design) to 11-14 days of renzapride (1, 2, or 4 mg) or placebo, once daily. Daily bowel habits and weekly satisfactory relief of IBS symptoms were recorded. At the end of treatment, gastric emptying (GE), small bowel transit (SBT), and colon transit (CT) were measured by scintigraphy. The relationship between CT and bowel function was evaluated. RESULTS: A statistically significant linear dose response to renzapride was detected for CT (GC8 h, P = 0.004; GC24 h, P = 0.056), and ascending colon (AC) emptying t1/2 (P = 0.019), but not for GE (t1/2, P = 0.088; or SBT, P = 0.41). AC half-time transit (t1/2) for placebo and 4 mg of renzapride were (median) 17.5 vs. 5.0 hours, respectively. Improved bowel function scores (stool form and ease of passage, but not frequency) were significantly (P < 0.05) associated with accelerated CT. Pharmacokinetic analysis showed linear kinetics of renzapride with a mean t1/2 in plasma of 10 hours. Bowel function and satisfactory relief were not significantly altered by renzapride, although a type II error cannot be excluded. No significant adverse clinical, laboratory, or electrocardiogram (ECG) effects were observed. CONCLUSIONS: Renzapride causes clinically significant dose-related acceleration of CT, particularly ascending colonic emptying; this acceleration of transit is associated with improvement of bowel function in female C-IBS patients.     

Gender differences in irritable bowel syndrome

In the United States and other Western cultures, a greater number of women seek health care services for symptoms of functional pain disorders, including irritable bowel syndrome, than men. Recent clinical trials indicate that gender differences in responsiveness to drug therapy also occur. Several lines of inquiry have focused on explaining this gender-related difference due to the higher prevalence of these disorders in women. Evidence of a physiologic component is based on gender differences in gastrointestinal transit time, visceral sensitivity, central nervous system pain processing, and specific effects of estrogen and progesterone on gut function. Additional factors may play a role, including gender-related differences in neuroendocrine, autonomic nervous system, and stress reactivity, which are related to bowel function and pain. However, the link between these measures and gut motility or sensitivity remains to be clarified. Psychological characteristics, including somatization, depression, and anxiety as well as a history of sexual abuse, may also contribute to gender-related differences in the prevalence of irritable bowel syndrome. Although gender differences in the therapeutic benefit of serotonergic agents have been observed, less is known about potential differences in responsiveness to nondrug therapies for irritable bowel syndrome.     

Comparison of colonic transit time between patients with constipation-predominant irritable bowel syndrome and functional constipation

Background/Aim  

Functional constipation (FC) and constipation-predominant IBS (C-IBS) are two main subtypes of constipation. Using radio-opaque markers is an easy and cost effective method to measure colonic transit time (CTT). We designed this study to compare the CTT between these two groups of constipated patients.     

Association between anxiety and quality of life in different subgroups irritable bowel syndrome

Introduction: Irritable Bowel Syndrome (IBS) is a frequent functional digestive disorder. Several studies have established the relationship between IBS and anxiety. Also it has been described a negative impact on quality of life in patients who suffer it, but in our country none of these studies have used ROME III criteria for evaluation. Objective: To know the frequency of anxiety in the different subgroups of IBS and its impact on quality of life. Methods: The study was conducted in patients who attended for first time to the outpatient clinic of our hospital for ten months. Adult patients who met the criteria of IBS were included. We applied the SF-36 quality of life questionnaire and the Hamilton anxiety scale. Results: One hundred and two patients who met for IBS criteria were included, of which 85% had anxiety. The IBS-C was the most frequent subgroup. Divided by subgroups, found that 52%, 85.1%, 90% and 80.9% had anxiety for IBS-C, IBS-D, IBS-M and IBS-NC respectively, without significant difference between groups. Patients with anxiety had coger quality of life scores in the categories of physical health, mental health and change in the state of health, (54.2 ± 18 vs. 72 ± 16, 52.8 ± 20 vs. 74 ± 14, 48 ± 28 vs. 59 ± 32) with respect to tose who have no anxiety (p <0.0001, p <0.0001 and p<0.15 respectively). Conclusions: The anxiety was not associated to any subgroup in particular of IBS, the presence of this influenced adversely and significantly on the quality of life of patients who suffer it.