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.     

Pharmacologic therapy for the irritable bowel syndrome

The management of the irritable bowel syndrome (IBS) remains unsatisfactory. For abdominal pain, antispasmodics are, at best, of only modest efficacy. Tricyclic antidepressants in low dose are useful (with the number needed to treat being three), but side effects and patient concerns regarding use of a centrally acting agent for depression remain limitations. Selective serotonin reuptake inhibitors are of uncertain efficacy in IBS. Opioid agonists, especially loperamide, are useful for diarrhea but not for pain in IBS; rebound constipation also remains a problem. Bile salt sequestering agents are not of established value in IBS but seem to be useful clinically in a small group of IBS patients with diarrhea. Aloestron, a 5HT(3) antagonist, should be reserved, if available, for women with severe diarrhea predominant IBS who have failed to respond to conventional therapy, and started at a low dose. Fiber and bulking agents may help constipation in some trials, but the evidence that they are efficacious in IBS is equivocal; they are frequently prescribed as first-line drugs for IBS regardless of the primary bowel disturbance but often increase bloating, gas, and pain. Laxatives are not of established value in IBS but are often taken by patients with constipation predominant IBS. Tegaserod, a partial 5HT(4) agonist, is now available in the United States and other countries for use in women with IBS whose primary bowel symptom is constipation; its efficacy in men and in those with alternating bowel habits is unknown. Probiotics are of uncertain efficacy. Chinese herbal medicine data are insufficient. Other new drugs in development include the cholecystokinin antagonists and novel visceral analgesics. Both current and potential therapies for IBS are reviewed in this article.     

New insights into visceral hypersensitivity--clinical implications in IBS

A subset of patients with IBS have visceral hypersensitivity and/or somatic hypersensitivity. Visceral hypersensitivity might have use as a clinical marker of IBS and could account for symptoms of urgency for bowel movements, bloating and abdominal pain. The mechanisms that lead to chronic visceral hypersensitivity in patients who have IBS are unclear. However, several working models may be considered, including: nociceptive input from the colon that leads to hypersensitivity; increased intestinal permeability that induces a visceral nociceptive drive; and alterations in the expression of microRNAs in gastrointestinal tissue that might be delivered via blood microvesicles to other target organs, such as the peripheral and/or central nervous system. As such, the chronic visceral hypersensitivity that is present in a subset of patients with IBS might be maintained by both peripheral and central phenomena. The theories underlying the development of chronic visceral hypersensitivity in patients with IBS are supported by findings from new animal models in which hypersensitivity follows transient inflammation of the colon. The presence of somatic hypersensitivity and an alteration in the neuroendocrine system in some patients who have IBS suggests that multisystemic factors are involved in the overall disorder. Thus, IBS is similar to other chronic pain disorders, such as fibromyalgia, chronic regional pain disorder and temporomandibular joint disorder, as chronic nociceptive mechanisms are activated in all of these disorders.     

Brain responses to visceral and somatic stimuli in patients with irritable bowel syndrome with and without fibromyalgia

OBJECTIVE: Symptoms of irritable bowel syndrome (IBS) and fibromyalgia (FM) commonly coexist. We hypothesized that one of the mechanisms underlying this comorbidity is increased activation of brain regions concerned with the processing and modulation of visceral and somatic afferent information, in particular subregions of the anterior cingulate cortex (ACC). METHODS: Regional cerebral blood flow (rCBF) was assessed in age-matched female IBS (n = 10) and IBS + FM (n = 10) subjects using H(2)(15)O positron emission tomography during noxious visceral (rectal) and somatic pressure stimuli. RESULTS: GI symptom severity was significantly higher in the IBS patients compared with the IBS + FM patients (p < 0.05). In addition, IBS + FM patients rated somatic pain as more intense than their abdominal pain (p < 0.05). Whereas the somatic stimulus was less unpleasant than the visceral stimulus for IBS patients without FM, the somatic and visceral stimuli were equally unpleasant in the IBS + FM group. Group differences in regional brain activation were entirely within the middle subregion of the ACC. There was a greater rCBF increase in response to noxious visceral stimuli in IBS patients and to somatic stimuli in IBS + FM patients. CONCLUSION: Chronic stimulus-specific enhancement of ACC responses to sensory stimuli in both syndromes may be associated with cognitive enhancement of either visceral (IBS) or somatic (IBS + FM) sensory input and may play a key pathophysiologic role in these chronic pain syndromes.     

一氧化氮能神经调节异常在腹泻型肠易激综合征患者中的作用

目的　探讨一氧化氮 (NO)在肠易激综合征 (IBS)发病机制中的作用 ,并从基因水平揭示NO含量改变的原因。方法　 (1)应用电子气压泵及灌注导管测压仪研究 2 5例腹泻型IBS患者及 15例正常志愿者的肛门、直肠压力、直肠顺应性、乙状结肠和直肠运动指数以及直肠对容量刺激的感觉阈值 ;(2 )应用硝酸还原酶法测定两组肠黏膜NO的含量 ;(3)NADPH黄递酶组化法和计算机图像分析系统对两组肠黏膜肌层一氧化氮合酶 (NOS)阳性神经纤维作定量分析 ;(4)采用荧光定量PCR(FQ PCR)方法对神经型一氧化氮合酶 (nNOS)的基因表达进行定量分析。结果　 (1)肠道测压 :IBS患者的直肠静息压、肛管上部静息压、收缩压、松弛压、肛管下部静息压、收缩压、松弛压和直肠顺应性与正常人比较 ,差异无显著性 (P >0 .0 5 ) ;患者乙状结肠和直肠运动指数明显高于正常人 (P <0 .0 5 ) ;(2 )直肠内脏感觉阈值 :最低感觉阈值、排便阈值和疼痛阈值明显低于正常人 (P <0 .0 5 ) ;(3)肠黏膜NO含量 :患者结肠黏膜NO含量显著低于正常人 ,并且患者的NO含量与运动指数成负相关 ,与感觉阈值、排便阈值、疼痛阈值呈正相关 (P <0 .0 5 ) ;(4)NADPH组化染色 :IBS患者黏膜肌层NOS阳性神经纤维的面积和平均吸光度较正常人显著减少 (P <0 .0 5 ) ;(5 )NOS mRNA     

Sex-related differences in IBS patients: central processing of visceral stimuli

BACKGROUND & AIMS: Women have a higher prevalence of irritable bowel syndrome (IBS) and possible differences in response to treatment, suggesting sex-related differences in underlying pathophysiology. The aim of this study was to determine possible sex-related differences in brain responses to a visceral and a psychological stressor in IBS. METHODS: Regional cerebral blood flow measurements using H(2)(15)O positron emission tomography were compared across 23 female and 19 male nonconstipated patients with IBS during a visceral stimulus (moderate rectal inflation) and a psychological stimulus (anticipation of a visceral stimulus). RESULTS: In response to the visceral stimulus, women showed greater activation in the ventromedial prefrontal cortex, right anterior cingulate cortex, and left amygdala, whereas men showed greater activation of the right dorsolateral prefrontal cortex, insula, and dorsal pons/periaqueductal gray. Similar differences were observed during the anticipation condition. Men also reported higher arousal and lower fatigue. CONCLUSIONS: Male and female patients with IBS differ in activation of brain networks concerned with cognitive, autonomic, and antinociceptive responses to delivered and anticipated aversive visceral stimuli.     

抗抑郁药治疗肠易激综合征的研究进展

目前研究发现精神心理因素在肠易激综合征（IBS）的发病中起重要作用,抗抑郁药在治疗IBS中的作用已受到越来越多的关注。常用的抗抑郁药包括选择性5-羟色胺再摄取抑制剂（SSRIs）、三环类抗抑郁药（TCAs）、5-羟色胺和去甲。肾上腺素再摄取抑制剂（SNRIs）等。本文就近年抗抑郁药治疗IBS的研究进展作一综述。     

Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome

The pathophysiology of irritable bowel syndrome(IBS) is not completely understood. However, several factors are known to play a role in pathophysiology of IBS such as genetics, diet, gut microbiota, gut endocrine cells,stress and low-grade inflammation. Understanding the pathophysiology of IBS may open the way for new treatment approaches. Low density of intestinal stem cells and low differentiation toward enteroendocrine cells has been reported recently in patients with IBS. These abnormalities are believed to be the cause of the low density of enteroendocrine cells seen in patients with IBS.Enteroendocrine cells regulate gastrointestinal motility, secretion, absorption and visceral sensitivity. Gastrointestinal dysmotility, abnormal absorption/secretion and visceral hypersensitivity are all seen in patients with IBS and haven been attributed to the low density the intestinal enteroendocrine cells in these patients.The present review conducted a literature search in Medline(Pub Med) covering the last ten years until November 2019, where articles in English were included.Articles about the intestinal stem cells and their possible role in the pathophysiology of IBS are discussed in the present review. The present review discusses the assumption that intestinal stem cells play a central role in the pathophysiology of IBS and that the other factors known to contribute to the pathophysiology of IBS such as genetics, diet gut microbiota, stress, and lowgrade inflammation exert their effects through affecting the intestinal stem cells.It reports further the data that support this assumption on genetics, diet, gut microbiota, stress with depletion of glutamine, and inflammation.     

The irritable bowel syndrome

The irritable bowel syndrome (IBS) is a familiar problem in the clinic, but as a disease entity it remains ill defined. Much confusion has arisen in the past, because of the inappropriate inclusion within the category of IBS of almost any patient with unexplained abdominal discomfort. Recent work has established that IBS patients can be positively identified by a cluster of specific symptoms. With the use of these criteria, it seems likely that IBS patients suffer from a diffuse motor abnormality of the gut associated with visceral hypersensitivity; although there is no associated psychopathology, a central nervous system component to the disorder is possible. Better insight into IBS promises more effective management.     

Is it diverticular disease or is it irritable bowel syndrome?

Symptomatic diverticular disease (SYMP-DD) and irritable bowel syndrome (IBS) share many features. Both are characterised by recurrent episodes of abdominal pain which may be slightly more frequent in IBS than SYMP-DD. They may also both exhibit an erratic bowel habit with diarrhoea, constipation and alternating types. It is important to assess anxiety, depression and somatisation since this can be increased in both types of patients and may be associated with visceral hypersensitivity. There are also significant differences between IBS and SYMP-DD. In particular, SYMP-DD patients are older, lack the female predominance seen in IBS and may often have fever with prolonged episodes of pain. For them, abnormalities of the gut are probably more important than cerebral factors, while for IBS the reverse is true. Treatments should be directed at the predominant abnormality which will vary in every patient.     

Novel techniques to study visceral hypersensitivity in irritable bowel syndrome

Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms of irritable bowel syndrome (IBS), and it has been proposed as a “biologic marker” for the condition. Visceral hypersensitivity can be influenced by peripheral and central mechanisms affecting pain perception. The optimal method for its assessment in humans has not been determined. Current techniques include stimulation via the computerized barostat and electrical stimulation, response measures including the lower limb reflex, and brain imaging modalities such as functional MRI and positron emission tomography. It has been shown that IBS patients have decreased sensory thresholds to colonic and rectal balloon distention by barostat. Studies using electrical stimulation and the RIII lower limb reflex have further confirmed enhanced visceral perception in IBS. Evidence from more recent neuroimaging studies suggests that IBS patients have abnormal activation of brain circuits involved in emotional and cognitive modulation of sensory information, resulting in ineffective pain modulation; these circuits may have a pathophysiologic role in enhancing visceral perception. There are few effective pharmacologic treatments that relieve IBS symptoms, and improved understanding of brain-gut interactions and factors relating to enhanced visceral perception may guide us in developing more efficacious treatments.     

Gene, environment, and brain-gut interactions in irritable bowel syndrome

The genetic predisposition and influence of environment may underlie in the pathogenesis and/or pathophysiology of irritable bowel syndrome (IBS). This phenomenon, gene x environment interaction together with brain-gut interactions is emerging area to be clarified in IBS research. Earlier studies focused on candidate genes of neurotransmitters, cytokines, and growth factors. Among them, some studies but not all studies revealed association between phenotypes of IBS and 5-hydroxytryptamine (5-HT)-related genes, noradrenaline-related genes, and cytokine genes. Recent prospective cohort study showed that genes encoding immune and adhesion molecules were associated with post-infectious etiology of IBS. Psychosocial stressors and intraluminal factors especially microbiota are keys to develop IBS. IBS patients may have abnormal gut microbiota as well as increased organic acids. IBS is disorder that relates to brain-gut interactions, emotional dysregulation, and illness behaviors. Brain imaging with or without combination of visceral stimulation enables us to depict the detailed information of brain-gut interactions. In IBS patients, thalamus, insula, anterior cingulate cortex, amygdala, and brainstem were more activated in response to visceral stimulation than controls. Corticotropin-releasing hormone and 5-HT are the candidate substances which regulate exaggerated brain-gut response. In conclusion, gene x environment interaction together with brain-gut interactions may play crucial roles in IBS development. Further fundamental research on this issue is warranted.     

Centrally acting agents and visceral sensitivity

The evidence relating to the site and mechanism of action of "centrally acting" agents which may affect visceral sensitivity is reviewed. Antidepressant drugs such as amitriptyline as well as the newer selective serotonin reuptake inhibitors are thought to act at the level of the CNS. Opiates, including morphine as well as compounds such as trimebutine or fedotozine designed for therapeutic use in irritable bowel syndrome, are effective in reducing visceral nociception. Cytokines in the CNS are known to be involved in the modulation of pain and there is also evidence to suggest that centrally acting cytokines may play a role in the production of visceral hypersensitivity. Consequently, they may provide an interesting target for future research.     

Acupuncture for functional gastrointestinal disorders

Functional gastrointestinal (GI) symptoms are common in the general population. Especially, motor dysfunction of the GI tract and visceral hypersensitivity are important. Acupuncture has been used to treat GI symptoms in China for thousands of years. It is conceivable that acupuncture may be effective in patients with functional GI disorders because it has been shown to alter acid secretion, GI motility, and visceral pain. Acupuncture at the lower limbs (ST-36) causes muscle contractions via the somatoparasympathetic pathway, while at the upper abdomen (CV-12) it causes muscle relaxation via the somatosympathetic pathway. In some patients with gastroesophageal reflux disease (GERD) and functional dyspepsia (FD), peristalsis and gastric motility are impaired. The stimulatory effects of acupuncture at ST-36 on GI motility may be beneficial to patients with GERD or FD, as well as to those with constipation-predominant irritable bowel syndrome (IBS), who show delayed colonic transit. In contrast, the inhibitory effects of acupuncture at CV-12 on GI motility may be beneficial to patients with diarrhea-predominant IBS, because enhanced colonic motility and accelerated colonic transit are reported in such patients. Acupuncture at CV-12 may inhibit gastric acid secretion via the somatosympathetic pathway. Thus, acupuncture may be beneficial to GERD patients. The antiemetic effects of acupuncture at PC-6 (wrist) may be beneficial to patients with FD, whereas the antinociceptive effects of acupuncture at PC-6 and ST-36 may be beneficial to patients with visceral hypersensitivity. In the future, it is expected that acupuncture will be used in the treatment of patients with functional GI disorders.     

Sex differences of brain serotonin synthesis in patients with irritable bowel syndrome using alpha-[11C]methyl-L-tryptophan, positron emission tomography and statistical parametric mapping.

BACKGROUND: Irritable bowel syndrome (IBS) is the most common functional bowel disorder and has a strong predominance in women. Recent data suggest that the brain may play an important role in the pathophysiology of IBS in the brain-gut axis. It is strongly suspected that serotonin (5-HT), a neurotransmitter found in the brain and gut, may be related to the pathophysiology of IBS. It is reported that a 5-HT3 antagonist is effective only in female patients with diarrhea-predominant IBS. OBJECTIVE: In the present study, 5-HT synthesis was measured using positron emission tomography, with alpha-[11C]methyl-L-tryptophan as the tracer, in patients with IBS. The aim of the present study was to compare 5-HT synthesis in the IBS patients with that in the controls, and to compare 5-HT synthesis between male and female IBS patients. METHODS: Six male and six female nonconstipated IBS patients were scanned. Age-matched healthy volunteers were scanned as controls. Eighty minute dynamic scans were performed. Functional 5-HT synthesis images were analyzed using statistical parametric mapping. RESULTS: 5-HT synthesis was greater only in the female IBS patients in the right medial temporal gyrus (multimodal sensory association cortex) compared with the female controls (P<0.001). CONCLUSIONS: The greater brain 5-HT synthesis in the female IBS patients than in the controls may be related to the pathological visceral pain processing of the IBS patients, a larger female predominance of the disorder, and the sex difference of the efficacy of the 5-HT3 antagonist in treatment.     

Enhanced preattentive central nervous system reactivity in irritable bowel syndrome

OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder characterized by enhanced perceptual sensitivity and hypervigilance toward afferent signals from the viscera. We hypothesize that the increased responsiveness of IBS patients is a generalized phenomenon applying to stimuli other than visceral and attempt to demonstrate increased responsiveness to sounds as measured by the P1 scalp potential. METHODS: Event-related potentials were recorded from IBS patients and control subjects in an auditory task requiring detection of rare pitch targets in a designated ear. Visual words served as targets in an additional block. RESULTS: Compared to control subjects, IBS patients displayed a robust increase in the amplitude of the P1 scalp potential elicited by both attended and unattended sounds. CONCLUSIONS: Enhanced P1 indicates preattentive central nervous system dishabituation in response to repeated sounds. A generalized preattentive increase in central nervous system reactivity may be a feature that IBS shares with several anxiety disorders that frequently co-occur in these patients.     

Noncardiac chest pain

Opinion statement Noncardiac chest pain (NCCP) is a common condition with significant morbidity and economic implications. Psychological factors, gastroesophageal reflux disease (GERD), alteration in pain perception, and esophageal dysmotility play an important role in the pathogenesis of the disorder. Proton pump inhibitor (PPI) therapy is the most effective medical intervention for the treatment of GERD-related NCCP, as well as the most costeffective diagnostic strategy for this condition. Pain modulators such as tricyclic antidepressants, trazodone, and selective serotonin reuptake inhibitors infer a visceral analgesic effect and consequently are the treatment of choice for patients with non-GERD-related NCCP. Furthermore, cognitive behavioral therapy has also been shown to be useful in the management of subset of patients with non-GERD-related NCCP. Newer therapeutic modalities and interventions such as lower esophageal sphincter injection of botulinum toxin in NCCP patients with spastic esophageal motility disorders, theophylline, and 5-HT4 receptor agonists may supplement or replace current treatment for non-GERD-related NCCP. Future compounds may include new visceral analgesics or medications that interfere with the development of peripheral or central sensitization.     

Motility disorders in the irritable bowel syndrome

Specific abnormalities of colonic and small bowel motility are identifiable and associated with symptoms in IBS. Characteristic abnormalities in colonic motility include a prolonged increase in 3-cycles/min colonic motor activity after a meal, an exaggerated increase in 3-cycles/min motor activity in response to stressors and CCK, and increased visceral sensitivity and motor activity in response to balloon distention. Symptoms in patients with IBS correlate in some cases with the abnormal gastrocolonic response and with pain induced by distention at various sites in the colon. Small bowel motility abnormalities identified reproducibly in IBS include an increase in daytime jejunal DCCs, an increase in daytime ileal PPCs, and more frequent cycling of daytime MMCs (in diarrhea-predominant IBS only). DCCs and PPCs are strongly associated with symptoms in IBS, and PPCs associated with altered ileocecal transit may be an important mechanism of symptoms in some patients with IBS. Esophageal and gastroduodenal motility abnormalities are inconsistently identified in IBS, and most symptoms in IBS appear to be secondary to small bowel or colonic dysfunction. Because of the paroxysmal nature of these motor abnormalities in IBS, prolonged motility recordings are required to better understand the pathophysiology of this syndrome. Patients with IBS may have altered visceral sensation and changes in afferent reflex mechanisms that modulate GI motility. These patients do not have a generalized increase in pain perception, but may have a distinct sensitivity to visceral afferent stimulation in both gastrointestinal and other viscera. Whether the altered "setpoint" to visceral afferent stimulation in IBS is intrinsic to the smooth muscle of viscera or secondary to CNS and ANS modulation is not known. Many of the symptoms and abnormalities of small bowel and colonic motility in IBS probably result from these changes in afferent sensation and reflex mechanisms. These findings support the concept that IBS is an abnormality of intestinal motility in conjunction with a "sensitive" gut.     

Sex specific alterations in autonomic function among patients with irritable bowel syndrome

BACKGROUND: Irritable bowel syndrome (IBS) is associated with increased psychological symptoms, early life stressors, and alterations in visceral perception and brain responses to noxious visceral stimuli. The autonomic nervous system (ANS) is a likely mediator for these brain-gut interactions. The few studies directly examining ANS measures have been suggestive of alterations in some IBS patients, but no studies to date have examined the potentially critical variables of sex differences or response to visceral stimulation. AIMS: (1) To test differences in ANS function during rest and during a visceral stressor (rectosigmoid balloon distension) between IBS patients and healthy control subjects. (2) To examine the role of sex on the autonomic responses of IBS patients. METHODS: Baseline autonomic measures were evaluated from 130 Rome I positive IBS patients and 55 healthy control subjects. Data were also collected from a subset of 46 IBS patients and 16 healthy control subjects during a sigmoid balloon distension study. Heart rate variability measures of peak power ratio (PPR) and peak power high frequency (PPHF) were analysed to assess sympathetic balance and parasympathetic response, respectively. Peripheral sympathetic response was measured by skin conductance. RESULTS: IBS patients showed a greater skin conductance response to visceral distension than controls. IBS patients had higher PPR and lower PPHF across conditions. Male IBS patients had higher skin conductance and PPR than females and lower PPHF. CONCLUSIONS: IBS patients have altered autonomic responsiveness to a visceral stressor, with increased sympathetic and decreased parasympathetic activity. These differences are predominantly seen in males.     

Dexamethasone prevents visceral hyperalgesia but not colonic permeability increase induced by luminal protease-activated receptor-2 agonist in rats

BACKGROUND: Low-grade inflammation may play a role in the pathogenesis of irritable bowel syndrome (IBS). Although corticosteroids are potent inhibitors of inflammatory processes, only one study with corticosteroids in patients with postinfectious IBS exists, which suggests that prednisolone is not an effective treatment for IBS symptoms. AIM: To evaluate whether dexamethasone treatment prevents protease-activated receptor-2 (PAR-2) activation-induced visceral hyperalgesia and increased permeability in rats, and to determine whether the effects involve colonic mast cells. METHODS: Abdominal contractions provoked by rectal distension were recorded in rats equipped with intramuscular electrodes. Changes in visceral hypersensitivity provoked by intracolonic administration of PAR-2-activating peptide (SLIGRL; H-serine-leucine-isoleucine-glycine-arginine-leucine-OH), changes in colonic mucosal rat mast cell protease-II (RMCP-II) content, mast cell count and PAR-2 expression were measured after a 4-day treatment with dexamethasone (1 mg/day/rat intraperitoneally) or its vehicle (water). The effect of mast cell stabiliser (doxantrazole, 1 mg/kg intraperitoneally, 2 h before and 6 h after intracolonic infusion of SLIGRL) on SLIGRL-induced visceral hyperalgesia was also assessed. The effects of SLIGRL and a mast cell degranulator (compound 48/80) on the permeability of colonic strips from vehicle- or dexamethasone-treated rats were investigated in Ussing chambers. RESULTS: 4 days of dexamethasone as well as doxantrazole diminished the SLIGRL-induced hyperalgesia for all volumes of distension. This effect of dexamethasone was accompanied by a reduced responsiveness of colonic permeability to compound 48/80, and decreased RMCP-II content and mast cell number. Dexamethasone treatment did not influence colonic mucosal PAR-2 expression and permeability responsiveness to SLIGRL. CONCLUSIONS: Dexamethasone treatment improves PAR-2 agonist-induced visceral hypersensitivity but does not prevent PAR-2 agonist-induced increase in colonic permeability in rats. This effect is coupled with a reduction of colonic mast cell number and RMCP-II contents.