Anti-hyperalgesic effect of octreotide in patients with irritable bowel syndrome

BACKGROUND: Octreotide has been found to be beneficial in the treatment of chronic pain, although the mechanisms underlying its therapeutic effect are incompletely understood. AIMS: To assess the effect of octreotide on perceptual responses to rectal distension in irritable bowel syndrome patients and healthy controls at baseline and following the experimental induction of rectal hyperalgesia. METHODS: In study 1, rectal perception thresholds for discomfort were determined in seven irritable bowel syndrome patients and eight healthy controls on three separate days using a computer-controlled barostat. Subjects received saline, low-dose and high-dose octreotide in a random double-blind fashion. In study 2, perceptual responses to rectal distension were obtained in nine irritable bowel syndrome patients and seven controls before and after repetitive high-pressure mechanical sigmoid stimulation. RESULTS: Octreotide increased the discomfort thresholds in irritable bowel syndrome patients, but not in controls, without changing rectal compliance. Repetitive sigmoid stimulation resulted in decreased rectal discomfort thresholds in the patient group only. In irritable bowel syndrome patients, octreotide prevented the sensitizing effect of repetitive sigmoid stimulation on rectal discomfort thresholds. CONCLUSIONS: Octreotide effectively increased discomfort thresholds in irritable bowel syndrome patients, but not in controls, at baseline and during experimentally induced rectal hyperalgesia. These findings suggest that octreotide exerts primarily an anti-hyperalgesic rather than analgesic effect on visceral perception.     

Selective 5-hydroxytryptamine antagonism: a role in irritable bowel syndrome and functional dyspepsia?

Background: Abnormalities of gut motility and visceral pain perception are both thought to be involved in the pathogenesis of irritable bowel syndrome and may be susceptible to modulation by drugs affecting the various 5-HT receptor subtypes. The aim of this study was to investigate the therapeutic potential of a 5-HT₃ antagonist in irritable bowel syndrome.
Methods: Fifty patients with irritable bowel syndrome were treated with ondansetron, a highly selective 5-HT₃ antagonist, in a double-blind, placebo-controlled cross-over study. In addition to assessing its effect on the classical symptoms of irritable bowel syndrome (abdominal pain, distension and disordered bowel habit) its effect on symptoms often seen in irritable bowel syndrome, but more commonly associated with functional dyspepsia, was also examined.
Results: Ondansetron reduced bowel frequency ( P =0.035) and improved stool consistency ( P =0.002) in diarrhoea predominant irritable bowel syndrome and did not cause a deterioration of bowel habit in constipation predominant subjects. No statistically significant improvement was seen for abdominal pain or distension, although those patients who did respond were approximately twice as likely to be taking ondansetron than placebo. It was also found that ondansetron significantly improved the upper gastrointestinal symptoms of post-prandial epigastric discomfort ( P =0.008), flatulence ( P =0.022) and heartburn ( P =0.003).
Conclusion: The results of this study justify evaluation of the therapeutic potential of selective 5-HT antagonists in both functional dyspepsia and irritable bowel syndrome.     

Impact of advertisement and clinic populations in symptoms and perception of irritable bowel syndrome

BACKGROUND: This study assessed the impact of recruitment on irritable bowel syndrome clinical trials, by determining whether irritable bowel syndrome patients recruited from advertisement or a specialty clinic differ in clinical and physiologic measures. METHODS: We prospectively surveyed 657 irritable bowel syndrome patients who either: (i) were referred from a functional bowel disease clinic (52%); or (ii) responded to advertisement for clinical trials (48%), using questionnaires about bowel and psychological symptoms, and quality of life. In a subset of 42 irritable bowel syndrome patients (29 advertisement and 15 clinic patients), rectal discomfort thresholds were measured before and after repetitive sigmoid stimulation. RESULTS: While the advertisement population more commonly consulted primary care physicians, the clinic population more commonly consulted gastroenterologists. The clinic population reported more prevalent and severe abdominal pain, and higher psychological symptom scores, while the advertisement population had greater quality of life. In the visceral perception studies, both subgroups were hypersensitive to rectal distension. CONCLUSION: Compared to the clinic population, the advertisement population had less severe abdominal pain and psychological symptoms, better quality of life but similar visceral perception. The differences in clinical self-reports may have consequences for enrolment of these different patient populations into clinical trials.     

Antinociceptive potency of enkephalins and enkephalinase inhibitors in the mouse model of colorectal distension—proof‐of‐concept

Irritable bowel syndrome (IBS) is a chronic disease characterized by abdominal pain and changes in bowel habits. Patients with IBS comprise a significant portion of attendants at the outpatient clinics. Targeting intestinal opioid receptors was found successful in alleviating pain and diarrhea—two major symptoms of IBS. In this study, we aimed to evaluate a novel potential pharmacological option: the use of enkephalinase inhibitors in therapy of visceral pain occurring in the course of IBS. We thus assessed the antinociceptive efficacy of enkephalins: Leu‐enkephalin and Met‐enkephalin, and enkephalinase inhibitors: opiorphin and sialorphin in the mouse model of visceral pain induced by colorectal distension. Leu‐enkephalin, Met‐enkephalin, and sialorphin, but not opiorphin, at the dose of 1 mg/kg injected subcutaneously potently decreased the visceromotor response to colon distension as compared to control. To conclude, enkephalinase inhibitors are worth being considered as potential therapeutics in patients with chronic abdominal pain and/or changed bowel habits, that is, suffering from IBS.     

Post-inflammatory modification of colonic afferent mechanosensitivity

1. The present review discusses interactions between the immune and nervous systems in post-infectious irritable bowel syndrome (PI-IBS).
2. Visceral pain is the single symptom that most affects the quality of life of patients with irritable bowel syndrome (IBS), yet it is the least successfully managed. An underlying hypersensitivity of colonic afferents to mechanical stimuli has long been implicated in visceral pain in IBS, but little more is known of the physiological aetiology.
3. The PI-IBS patients are a cohort of IBS patients who attribute their symptoms to a preceding gastrointestinal infection by pathogens such as Campylobacter or Salmonella . Current evidence suggests that the immune system remains activated in these patients and contributes to their visceral hypersensitivity. This is characterized by a shift in the phenotype of circulating immune cells towards a Type 1 (Th1 predominating) state. Products from these immune cells sensitize colonic afferents to mechanical stimuli.
4. Rectal instillation of trinitrobenzene sulphonic acid induces a Th1-mediated inflammatory response, consistent with clinical observations in PI-IBS. The visceral hypersensitivity observed in this model is biphasic, with an initial onset characterized by visceral hypersensitivity correlating with histological damage followed by a delayed phase that occurs after histological recovery. Interestingly, this chronic visceral hypersensitivity is mediated by afferents in closest apposition to blood vessels, but furthest from the initial site of damage.
5. Both clinical and experimental evidence indicates that chronic dysregulation of the immune system induces visceral afferent hypersensitivity and, therefore, may be the central mechanism underlying PI-IBS.     

Alosetron

Alosetron is a potent and highly selective serotonin 5-HT3 receptor antagonist which has been evaluated for the management of irritable bowel syndrome (IBS). It blocked the fast 5HT3-mediated depolarisation of guinea-pig myenteric and submucosal neurons in vitro, with half-maximal inhibition at approximately 55 nmol/L. Alosetron attenuated the visceral nociceptive effect of rectal distension in conscious or anaesthetised dogs. It increased the compliance of the colon to distension in patients with IBS and delayed colonic transit in patients with IBS or carcinoid diarrhoea and in healthy volunteers. A single dose of alosetron 4 mg increased in vivo fluid absorption in normal human small intestine. In clinical trials in patients with IBS, alosetron 1 mg twice daily was effective in relieving abdominal pain and discomfort. Alosetron was most effective in female patients and particularly in those with diarrhoea-predominant IBS. In patients with IBS and healthy volunteers who received alosetron, the most common adverse event was constipation.     

Relationship between rectal sensitivity, symptoms intensity and quality of life in patients with irritable bowel syndrome

Background  Relationships between pain threshold during rectal distension and both symptoms intensity and alteration in quality of life (QoL) in irritable bowel syndrome (IBS) patients have been poorly evaluated.
Aim  To evaluate relationships between rectal sensitivity, IBS symptom intensity and QoL in a multicentre prospective study.
Methods  Rectal threshold for moderate pain was measured during rectal distension in IBS patients (Rome II), while IBS symptoms intensity was assessed by a validated questionnaire and QoL by the Functional Digestive Disorder Quality of Life questionnaire.
Results  Sixty-eight patients (44.2 ± 12.7 years, 48 women) were included. The mean rectal distending volume for moderate pain was 127 ± 35 mL while 45 patients (66%) had rectal hypersensitivity (pain threshold <140 mL). Rectal threshold was not significantly related either to overall IBS intensity score ( r  = −0.66, P  =   0.62) or to its different components, or to FDDQL score ( r  = 0.30, P  =   0.14). Among FDDQL domains, only anxiety ( r  = 0.30, P  =   0.01) and coping ( r  = 0.31, P  =   0.009) were significantly related with pain threshold.
Conclusions  In this study, two-thirds of IBS patients exhibited rectal hypersensitivity. No significant correlation was found between rectal threshold and either symptom intensity or alteration in QoL.     

Review article: abdominal bloating and distension in functional gastrointestinal disorders--epidemiology and exploration of possible mechanisms

Background A sensation of abdominal bloating, sometimes accompanied by an increase in girth (distension), is one of the most common and most intrusive features of functional bowel disorders. Aim To conduct a systematic, evidence‐based review of the epidemiology and pathophysiology of abdominal bloating and its relationship to distension. Methods The terms bloating, distension, functional bowel, irritable bowel syndrome, constipation and diarrhoea were searched on MEDLINE up to 2006. References from selected articles and relevant abstracts were also included. Results Approximately 50% of irritable bowel syndrome patients with bloating also experience an increase in abdominal girth and this is more pronounced with constipation than diarrhoea. Bloating appears to be more frequently associated with visceral hypersensitivity, whereas distension is more often related to hyposensitivity and delayed transit. Although there is little evidence for excessive gas as a cause of bloating, gas infusion studies suggest that handling of gas may be impaired in irritable bowel syndrome and there may also be abnormal relaxation of the anterior abdominal musculature in these patients. Conclusions There is unlikely to be a single cause for bloating and distension, which probably have different, but overlapping, pathophysiological mechanisms. Relieving constipation might help distension, but the treatment of bloating may need more complex approaches involving sensory modulation.     

Effect of asimadoline, a kappa opioid agonist, on pain induced by colonic distension in patients with irritable bowel syndrome

BACKGROUND: Visceral hypersensitivity plays a major role in irritable bowel syndrome pathophysiology. Opioid kappa receptors on afferent nerves may modulate it and be the target for new irritable bowel syndrome treatments. AIM: This study evaluated the effect of the kappa opioid agonist asimadoline on perception of colonic distension and colonic compliance in irritable bowel syndrome patients. METHOD: Twenty irritable bowel syndrome female patients (Rome II criteria; 40 +/- 13 years) and hypersensitivity to colonic distension (Pain threshold < or = 32 mmHg) were included in a randomized double-blind cross-over trial comparing the effect of a single oral dose of asimadoline 0.5 mg or placebo on sensory thresholds (defined as a constant and sustained sensation) elicited by left colon phasic distension (5 mmHg steps, 5 min) up to a sensation of abdominal pain. Colonic compliance was compared by the slope of the pressure-volume curves. RESULTS: On asimadoline, pain threshold (mean +/- s.d.) (29.8 +/- 7.2 mmHg) was higher than on placebo (26.3 +/- 7.8 mmHg), difference not statistically significant (P = 0.1756, ANOVA). Area under curve of pain intensity rated at each distension step was significantly lower on asimadoline (89.3 +/- 33.9, ANOVA) than on placebo (108.1 +/- 29.7) (P = 0.0411). Thresholds of perception of nonpainful distensions were not altered on asimadoline, as compared with placebo. Colonic compliance was not different on placebo and asimadoline. CONCLUSION: Asimadoline decreases overall perception of pain over a wide range of pressure distension of the colon in irritable bowel syndrome patients, without altering its compliance. These data suggest that further studies should explore the potential benefit of asimadoline in treatment of pain in irritable bowel syndrome patients.     

Neurokinin-1-receptor antagonism decreases anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome: a pilot study

Background Irritable bowel syndrome is characterised by chronic abdominal pain and frequent comorbid anxiety. The substance P/neurokinin‐1 receptor system is implicated in the regulation of both pain and anxiety, suggesting a potential therapeutic target in IBS. Aim To determine whether inhibition of the neurokinin‐1 receptor (NK1R) will change pain ratings and brain responses to experimental visceral pain and anxiety symptoms in women with IBS or not. Methods Rome II positive IBS women were recruited for a double‐blind, placebo‐controlled, cross‐over study of NK1R antagonist AV608. Treatment periods were 3 weeks with a 2‐week washout period. Functional MRI during a visceral distension paradigm was performed before first treatment and after treatment blocks. SPM8 was used to compare brain activity during painful and nonpainful visceral stimuli in regions associated with emotional arousal and interoception. Negative affect, anxiety symptoms and pain ratings were assessed. Results Eleven subjects completed the study and eight subjects provided fMRI data. AV608, compared with placebo, was associated with reduced anxiety, negative affect, and pain ratings. During AV608 treatment, the amygdala, hippocampus and anterior cingulate gyrus showed decreased activity during visceral distension. AV608 was also associated with decreases in activity in brain regions associated with interoception (posterior insula, anterior mid‐cingulate gyrus). Conclusions Chronic treatment with AV608 in IBS is associated with improved mood and pain ratings and activity of emotional arousal related brain regions. This suggests that further exploration of NK1R antagonists is warranted in visceral pain disorders, particularly in patients with comorbid anxiety symptoms.     

Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome

BACKGROUND: Visceral hypersensitivity is considered an important pathophysiological mechanism in irritable bowel syndrome, yet its relationship to symptoms is unclear. AIM: To detect possible associations between symptoms and the presence of hypersensitivity to rectal distension in patients with irritable bowel syndrome. METHODS: Ninety-two irritable bowel syndrome patients and 17 healthy volunteers underwent a rectal barostat study. The association between specific irritable bowel syndrome symptoms and the presence of hypersensitivity was examined using Area under the Receiver Operating Characteristic curves. RESULTS: Irritable bowel syndrome patients had significantly lower thresholds for discomfort/pain than healthy volunteers: 24 (18-30) and 30 (27-45) mmHg above minimal distending pressure, respectively. Forty-one patients (45%) showed hypersensitivity to rectal distension. Proportions of patients with different predominant bowel habits were similar in hypersensitive and normosensitive subgroups (diarrhoea predominant: 39 and 41%, respectively; alternating type: 27 and 28%, respectively; constipation predominant: 34 and 31%, respectively). Severe abdominal pain was more frequent in hypersensitive, compared with normosensitive patients (88% vs. 67%, P = 0.02), but none of the individual irritable bowel syndrome symptoms could accurately predict the presence of hypersensitivity, as assessed by Area under the Receiver Operating Characteristic curve analysis. CONCLUSIONS: Hypersensitive and normosensitive irritable bowel syndrome patients present with comparable, heterogeneous symptomatology. Therefore, selection based on clinical parameters is unlikely to discriminate individual irritable bowel syndrome patients with visceral hypersensitivity from those with normal visceral sensitivity.     

香砂六君子汤治疗肠易激综合征的探讨

目的:肠易激综合征(Irrltable Bowel Syndrome,IBS)是一种以肠道功能混乱为主要特征的慢性疾病,临床表现比较复杂、呈多样性,症状主要为结肠症状,同时还可以伴有躯体症状或其他消化道症状。它是一种消化道免疫系统障碍性综合征,症状为长期或者反复发作的腹痛、腹胀、伴有排便习惯和大便性状异常,就目前而言尚缺乏形态学、细菌学和生化学指标。其确切病因和发病机制至今还未完全阐明,其涉及的因素较多,可能与肠道感染、胃肠运动紊乱、内脏感觉异常、精神心理障碍有关,从动力、心理、感觉、炎症、免疫和激素等方面研究十分广泛,至今未达成共识。而香砂六君子汤作为治疗肠易激综合征有效的一种复方,目前的研究也很有限。本文主要从中医治疗肠易激综合征的病因病机及治法方面切入探讨一下香砂六君子汤对此类疾病治疗的看法。方法:通过对肠易激综合征的病因病机和整体论治以及辨病分型论治的讨论,用以法统方的原则分析香砂六君子汤是否体现肠易激综合征的治法。结果:香砂六君子汤的配伍组方完美体现了肠易激综合征的治法。结论:为香砂六君子汤物质基础研究和临床治疗肠易激综合征提供了理论基础。     

Drug treatment of the irritable bowel syndrome.

Irritable bowel syndrome (IBS) is defined as a functional bowel disorder in which abdominal pain is associated with defecation or a change in bowel habit, and with features of disordered defecation and distension. The irritable bowel syndrome occurs in 10 to 20% of people worldwide and is very commonly encountered in clinical practice. This has encouraged the pharmaceutical industry to search for effective drug therapy. So far, a universally effective agent has not been found, and since this is a chronic, benign disorder, beginning in youth, long term drug use should be avoided. Nevertheless, if a specific IBS symptom, such as constipation or abdominal pain dominates, a specific drug may be helpful. However, tests and treatment should be minimised or even avoided in order to do no harm. A largely nonpharmaceutical approach to IBS should be taken. This approach employs drugs sparingly and then only targeted at specific and resistant symptoms.     

The serotonin reuptake inhibitor citalopram does not affect colonic sensitivity or compliance in rats

Altered serotonin signaling has been implicated in the pathophysiology of irritable bowel syndrome (IBS). Selective serotonin reuptake inhibitors (SSRI) improve IBS symptoms, although the mechanism of action remains unclear. We assessed the effects of the SSRI, citalopram, on colonic sensitivity and compliance in rats after acute and repeated administration. Colorectal distension was performed in conscious rats. Pressure–volume relationships during colorectal distension (2–20 mmHg), fitted using a power exponential model [Vol = V_max × exp[− (κ × RelP)^β], were used as a measure of colonic compliance. The visceral pain-related visceromotor response during colorectal distension (10–80 mmHg) was used to assess visceral sensitivity. Pressure–volume curves and visceromotor responses were assessed after acute citalopram (3 or 10 mg/kg, ip) or vehicle and after repeated treatment (7 and 14 days; 3 or 10 mg/kg/day). In vehicle-treated animals, pressure–volume curves were similar over time. Citalopram (acute or repeated treatment) did not affect neither the pressure–volume curves nor the visceromotor response to colorectal distension. Thus, citalopram, after acute or repeated administration, had no significant effects on colon compliance or visceral pain during colorectal distension in rats. These results agree with recent observations in humans suggesting that the therapeutic actions of citalopram in IBS are independent of any effects on colonic sensorimotor function.     

Review article: the functional abdominal pain syndrome

Aliment Pharmacol Ther 2011; 33: 514–524

Summary

Background Functional abdominal pain syndrome (FAPS) is a debilitating disorder with constant or nearly constant abdominal pain, present for at least 6 months and loss of daily functioning. Aim To review the epidemiology, pathophysiology and treatment of FAPS. Methods A literature review using the keywords: functional abdominal pain, chronic abdominal pain, irritable bowel syndrome and functional gastrointestinal disorders. Results No epidemiological studies have focused specifically on FAPS. Estimates of prevalence range from 0.5% to 1.7% and tend to show a female predominance. FAPS pathophysiology appears unique in that the pain is caused primarily by amplified central perception of normal visceral input, rather than by enhanced peripheral stimulation from abdominal viscera. The diagnosis of FAPS is symptom‐based in accordance with the Rome III diagnostic criteria. These criteria are geared to identify patients with severe symptoms as they require constant or nearly constant abdominal pain with loss of daily function and are differentiated from IBS based on their non‐association with changes in bowel habit, eating or other gut‐related events. As cure is not feasible, the aims of treatment are reduced suffering and improved quality of life. Treatment is based on a biopsychosocial approach with a therapeutic patient–physician partnership at its base. Therapeutic options include central nonpharmacological and pharmacological modalities and peripheral modalities. These can be combined to produce an augmentation effect. Conclusion Although few studies have assessed functional abdominal pain syndrome or its treatment specifically, the treatment strategies outlined in this paper appear to be effective.     

Effect of long-term treatment with octreotide on rectal sensitivity in patients with non-constipated irritable bowel syndrome

BACKGROUND: Acute administration of octreotide reduces visceral perception and therefore has been suggested as potential treatment for irritable bowel syndrome. Whether prolonged treatment with octreotide also reduces visceral sensitivity and improves gastrointestinal symptoms remains, however, unknown. AIM: To investigate the effect of a slow release preparation of octreotide on rectal sensitivity and symptoms in irritable bowel syndrome patients. METHODS: Forty-six non-constipated irritable bowel syndrome patients (52% female, 19-63 years) participated. Before and after 8 weeks of treatment with octreotide (Sandostatin LAR 20 mg i.m.) or placebo, patients underwent a barostat study to assess the rectal sensitivity. During a 2-week run-in period and treatment, abdominal pain, defecation frequency, consistency and symptom relief were scored weekly. RESULTS: Octreotide, but not placebo, significantly increased the threshold for first sensation. Thresholds for urge to defecate and discomfort/pain and rectal compliance were not altered by either treatment. Octreotide improved stool consistency compared with placebo (loose stools after eight weeks: octreotide: 52%, placebo: 81%, P < 0.05). In contrast, abdominal pain and defecation frequency were not affected. CONCLUSIONS: Although the threshold of first rectal sensation increased and stool consistency improved, long-term treatment with octreotide, at least at the current dose used, has no visceral analgesic effect and fails to improve irritable bowel syndrome symptoms.     

CRF1 receptors as a therapeutic target for irritable bowel syndrome

The characterization of the corticotropin-releasing factor (CRF) family of neuroendocrine regulatory peptides, the cloning and pharmacological characterization of two CRF receptor subtypes (CRF(1) and CRF(2)), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress and the potential involvement of the CRF system in different pathophysiological conditions, including functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and psychopathologies such as anxiety/depression. Compelling pre-clinical data showed that brain CRF administration mimics acute stress-induced colonic responses and enhances colorectal distension-induced visceral pain in rats through CRF(1) receptors. Similarly, peripheral CRF reduced the pain threshold to colonic distension and increased colonic motility in humans and rodents. These observations mimic the manifestations of IBS, characterized by abdominal bloating/discomfort and altered bowel habits. Moreover, CRF-CRF(1) pathways have been implicated in the development of anxiety/depression. These psychopathologies, together with stressful life events, have high comorbidity with IBS, and are considered significant components of the disease. From these observations, CRF(1) receptors have been suggested as a target to treat IBS. Peripherally acting CRF(1) antagonists might directly improve IBS symptoms, as related to motility, secretion and immune response. On the other hand, central actions will be beneficial as to prevent the psychopathologies that co-exist with IBS and as a way to modulate the central processing of stress- and visceral pain-related signals. Here, we review the pre-clinical and clinical data supporting these assumptions, and address the efforts done at a pharmaceutical level to develop effective therapies targeting CRF(1) receptors for functional gastrointestinal disorders.     

Review article: new receptor targets for medical therapy in irritable bowel syndrome

Background  Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for irritable bowel syndrome (IBS) trials have enhanced interest as new targets for medical therapy are proposed based on novel mechanisms or chemical entities.
Aims  To review the approved lubiprostone, two targets that are not meeting expectations (tachykinins and corticotrophin-releasing hormone), the efficacy and safety of new 5-HT₄ agonists, intestinal secretagogues (chloride channel activators, and guanylate cyclase-C agonists), bile acid modulation, anti-inflammatory agents and visceral analgesics.
Methods  Review of selected articles based on PubMed search and clinically relevant information on mechanism of action, safety, pharmacodynamics and efficacy.
Results  The spectrum of peripheral targets of medical therapy addresses chiefly the bowel dysfunction of IBS and these effects are associated with pain relief. The pivotal mechanisms responsible for the abdominal pain or visceral sensation in IBS are unknown. The new 5-HT₄ agonists are more specific than older agents and show cardiovascular safety to date. Secretory agents have high specificity, low bioavailability and high efficacy. The potential risks of agents 'borrowed' from other indications (such as hyperlipidaemia, inflammatory bowel disease or somatic pain) deserve further study.
Conclusions  There is reason for optimism in medical treatment of IBS with a spectrum of agents to treat bowel dysfunction. However, visceral analgesic treatments are still suboptimal.     

消化门诊肠易激综合征患者肠外症状分析

目的了解肠易激综合征(IBS)患者临床症状表现,尤其是肠外症状,提高IBS诊断率。方法对2010年12月至2011年7月郑州大学第一附属医院消化内科门诊就诊并按照罗马Ⅲ标准诊断为IBS的患者进行问卷调查。共调查866例,收回问卷847份作为统计病例。结果 IBS是一种复杂的身心疾病,除表现在胃肠功能紊乱,腹痛、腹部不适,排便性状、频率改变外,还表现有咽部不适及异物感,口干、口苦、口臭、无味觉,功能性消化不良,无饥饿感,腰背及肌肉酸、痛、纤维肌痛综合征等全身不明原因的疼痛,手心、脚心灼热等功能性低热,肢体凉、畏寒,失眠、头痛,心烦,慢性疲劳综合征,体重减轻,尿道不适,性交困难等肠外表现等。结论 IBS患者多反复就诊于综合医院的各个科室,部分临床医生对IBS复杂的临床症状尤其是肠道外症状认识少,鉴别困难,使IBS诊断率低,治疗效果差。     

Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome

Background  Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response.
Aim  To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients.
Methods  Nineteen patients with IBS were given amitriptyline 25–50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity).
Results  Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders ( P  > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline −31% vs. +2%, P  < 0.03 respectively).
Conclusion  In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS.