Perceptual hyperreactivity to auditory stimuli in patients with irritable bowel syndrome

BACKGROUND: Patients with irritable bowel syndrome (IBS) have abnormal perception of visceral stimuli; however, no study has so far investigated the perception of non-visceral stimuli in IBS. In the present study we used event-related potentials (ERP) to study whether IBS patients differed from healthy controls in processing of auditory stimuli and, if so, how this was influenced by emotions. METHODS: We compared ERPs to auditory stimuli in 40 female diarrhoea-predominant IBS patients without current psychiatric illness with those in 20 healthy controls. Tones were used as standard and target stimuli, and words with emotional content as distractors. Characteristics of the first negative wave (N100) and mean amplitudes in 50-msec time intervals between 150 and 600 msec were assessed. RESULTS: At the frontal midline electrode IBS patients had significantly enhanced N100 amplitude to all stimuli, persisting after adjustment for age, current emotions, and personality traits. They additionally had enhanced waves 200-300 msec and 400-500 msec after stimulus. The latter differences disappeared after adjustment for emotions and personality traits. CONCLUSIONS: In the frontal brain region, IBS patients seem to have a hyperreactivity to auditory stimuli compared with controls. Later elements (P300, N400) of stimulus processing were influenced by emotions and personality traits. These may possibly contribute to changes in intestinal motility caused by stress. The study indicates that aberrant brain functioning may be an element of the irritable bowel syndrome. It may elucidate a mechanism for brain-gut interaction by which psychosocial stress may influence visceral pain perception in non-psychiatric subjects with an intestinal motility disorder and also the efficacy of psychiatric treatment on IBS symptoms.     

直肠内温度变化影响肠易激综合征患者内脏感觉阈值

目的 探讨直肠内温度及压力变化对肠易激综合征(IBS)患者内脏感觉阈值的影响，进一步研究IBS的发病机制。方法 通过直肠球囊内注入空气(压力刺激)、38℃温水、4℃冰水(温度刺激)及脐部放置冰袋加直肠球囊内充气，研究直肠温度和压力变化刺激对初始感觉阈值和排便阈值的影响。结果 (1)直肠球囊内注气后，IBS组患者的初始感觉阈值明显低于对照组，排便阈值差异不明显。IBS组中腹泻型与交替型患者的初始感觉阈值及排便阈值均明显降低；便秘型患者的初始感觉阈值稍低于对照组，排便阈值明显增高。(2)直肠球囊内注入4℃冰水后，除便秘型IBS的排便阈值稍有所增加外，其余患者初始感觉阈值及排便阈值均显著降低，以腹泻型变化最明显。(3)脐部放置冰袋可诱发部分患者产生症状，但对初始感觉阈值和排便阈值无明显影响。结论 直肠温度和压力刺激可明显降低IBS患者的初始感觉阈值和排便阈值，以腹泻型患者最显著。内脏对压力和温度的敏感性增高可能是IBS发病的重要机制之一。     

Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress

OBJECTIVES: Symptoms in irritable bowel syndrome (IBS) patients are sensitive to psychological stressors. These effects may operate through an enhanced responsiveness of the emotional motor system, a network of brain circuits that modulate arousal, viscerosomatic perception, and autonomic responses associated with emotional responses, including anxiety and anger. The aim of this study was to test the primary hypothesis that IBS patients show altered perceptual responses to rectal balloon distention during experimentally induced psychological stress compared with healthy control subjects. METHODS: A total of 15 IBS patients (nine women and six men) and 14 healthy controls (seven women and seven men) were studied during two laboratory sessions: 1) a mild stress condition (dichotomous listening to two conflicting types of music), and 2) a control condition (relaxing nature sounds). The stress and relaxation auditory stimuli were delivered over a 10-min listening period preceding rectal distentions and during the rectal distentions but not during the distention rating process. Ratings of intensity and unpleasantness of the visceral sensations, subjective emotional responses, heart rate, and neuroendocrine measures (norepinephrine, cortisol, adrenocorticotropic hormone [ACTH], and prolactin) were obtained during the study. RESULTS: IBS patients, but not healthy controls, rated the 45-mm Hg visceral stimulus significantly higher in terms of intensity and unpleasantness during the stress condition compared with the relaxation condition. IBS patients also reported higher ratings of stress, anger, and anxiety during the stress compared with the relaxing condition, whereas controls had smaller and nonsignificant subjective responses. Heart rate measurements, but not other neuroendocrine stress measures, were increased under the stress condition in both groups. CONCLUSION: These findings confirm the hypothesis of altered stress-induced modulation of visceral perception in IBS patients.     

Cerebral processing of auditory stimuli in patients with irritable bowel syndrome

AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To circumvent spinal viscerosomatic convergence mechanisms, we used auditory stimulation, and to identify a possible influence of psychological factors the stimuli differed in their emotional quality. METHODS: In 8 IBS patients and 8 controls, fMRI measurements were performed using a block design of 4 auditory stimuli of different emotional quality (pleasant sounds of chimes, unpleasant peep (2000 Hz), neutral words, and emotional words). A gradient echo T2*-weighted sequence was used for the functional scans. Statistical maps were constructed using the general linear model. RESULTS: To emotional auditory stimuli, IBS patients relative to controls responded with stronger deactiva-tions in a greater variety of emotional processing regions, while the response patterns, unlike in controls, did not differentiate between distressing or pleasant sounds. To neutral auditory stimuli, by contrast, only IBS patients responded with large significant activations. CONCLUSION: Altered cerebral response patterns to auditory stimuli in emotional stimulus-processing regions suggest that altered sensory processing in IBS may not be specific for visceral sensation, but might reflect generalized changes in emotional sensitivity and affective reactivity, possibly associated with the psychological comorbidity often found 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.     

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.     

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.     

Longitudinal change in perceptual and brain activation response to visceral stimuli in irritable bowel syndrome patients

BACKGROUND & AIMS: Symptom-related fears and associated hypervigilance toward visceral stimuli may play a role in central pain amplification and irritable bowel syndrome (IBS) pathophysiology. Repeated stimulus exposure leads to decreased salience of threat and reduction of hypervigilance. We sought to evaluate hypervigilance in IBS visceral hypersensitivity and associated brain activity. METHODS: Twenty IBS patients (14 female; moderate to severe symptoms) and 14 healthy controls participated in symptom and rectal distention assessments 6 times over 12 months. In a subset of 12 IBS patients, H2 15O-positron emission tomography images were obtained during baseline, rectal distentions, and anticipation of an aversive distention during the first and last session. Statistical parametric mapping (SPM99) was used to identify areas and networks activated during each session as well as those with differential activation across the 2 sessions. RESULTS: Perceptual ratings of the rectal inflations normalized over 12 months, whereas IBS symptom severity did not. There were no sex-related differences in these response patterns. Stable activation of the central pain matrix was observed over 12 months, and activity in limbic, paralimbic, and pontine regions decreased. During the anticipation condition, there were significant decreases in amygdala, dorsal anterior cingulate cortex, and dorsal brainstem activation at 12 months. Covariance analysis supported the hypothesis of changes in an arousal network including limbic, pontine, and cortical areas underlying the decreased perception seen over the multiple stimulations. CONCLUSIONS: In IBS patients, repeated exposure to experimental aversive visceral stimuli results in the habituation of visceral perception and central arousal, despite stable activation of networks processing visceral pain and its anticipation.     

便秘型肠易激综合征患者结、直肠肛门动力学的临床研究

目的研究便秘型肠易激综合征患者结肠、直肠动力,直肠感觉功能.方法用结肠传输试验检测结肠传输时间,并用结肠传输指数分型,用肛门直肠测压方法测定便秘型IBS直肠静息压,肛管静息压,肛门括约肌最大缩榨压,模拟排便时,直肠收缩压,肛门括约肌剩余压,直肠对容量扩张刺激的初始感觉阈值,最大耐受容量,直肠顺应性.结果便秘型IBS患者全结肠及各节段结肠传输时间均高于对照组,便秘型IBS患者肛管静息压,直肠静息压与对照组无差异(P＞0.05),肛门括约肌最大缩榨压低于正常对照组,最大耐受容量及直肠顺应性均明显高于对照组(P＜0.01),且发现不同传输类型的便秘型IBS肛门直肠测压表现不同.结论便秘型IBS患者存在结肠、肛门直肠动力及直肠感觉功能异常,结肠传输试验与肛门直肠测压相结合,可体现不同传输类型便秘型IBS肛门直肠动力学病因机制.     

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.     

Study on functional constipation and constipation‐predominant irritable bowel syndrome by using the colonic transit test and anorectal manometry

OBJECTIVE: To investigate the visceral perception, anorectal pressure and colonic transit time (CTT) in patients with functional constipation and constipation‐predominant irritable bowel syndrome (C‐IBS), and to study the manometric abnormalities of these two conditions. METHODS: The CTT in patients with functional constipation and C‐IBS was studied by using radiopaque markers. Rectal visceral perception thresholds, rectal compliance and anorectal pressure were examined by electric barostat. RESULTS: The CTT in both groups of constipated patients was abnormal. A lot of radiopaque markers remained in the right colon in C‐IBS patients, whereas in patients with functional constipation, the radiopaque markers remained in each segment of the colon. The anorectal resting pressure, squeezing pressure and relaxation pressure were normal in both groups. Rectal compliance and defecation thresholds were much higher compared with controls, and the rectal visceral perception of functional constipation was also abnormal. CONCLUSIONS: The motility abnormalities of functional constipation and C‐IBS occurred in different colonic segments. Results suggest that CTT measure­ment and anorectal manometry could be helpful in the differential diagnosis of these two conditions.     

Perceptual responses in patients with inflammatory and functional bowel disease

BACKGROUND AND AIMS: Enhanced visceral sensitivity following a transient inflammatory process in the gut has been postulated as an aetiological mechanism of irritable bowel syndrome (IBS). In this study we compared perceptual responses to rectosigmoid distension in patients with mild chronic inflammation of the rectum (ulcerative colitis (UC)) and patients without mucosal inflammation (IBS) to determine if chronic low grade mucosal inflammation may be a plausible explanation for rectosigmoid hypersensitivity reported in both IBS and UC patients. METHODS: UC disease activity was quantified using activity index scores. Perception thresholds for discomfort during rectosigmoid distension were compared between 11 UC patients with quiescent or mild disease activity, 18 IBS patients, and 13 healthy controls. RESULTS: Although UC activity index scores negatively correlated with perceptual thresholds for discomfort (r=-0.76, p=0.016), UC patients had higher discomfort thresholds compared with IBS patients and controls before (p=0.02) and after (p<0.001) a noxious sigmoid conditioning stimulus. CONCLUSIONS: Rectal perception was attenuated in UC but enhanced in IBS. In chronic mild inflammation, activation of antinociceptive mechanisms may prevent the development of visceral hyperalgesia. Low grade mucosal inflammation alone is unlikely to be responsible for symptoms in functional gastrointestinal disorders.     

Alterations of sensori-motor functions of the digestive tract in the pathophysiology of irritable bowel syndrome

Pathophysiology of irritable bowel syndrome (IBS) is based upon multiple factors that have been organised in a comprehensive model centred around the brain-gut axis. The brain-gut axis encompasses nerve pathways linking the enteric and the central nervous systems and contains a large proportion of afferent fibres. Functionally and anatomically, visceral nerves are divided in to two categories: the parasympathetic pathways distributing to the upper gut through the vagi and to the hindgut, through the pelvic and pudendal nerves, and the sympathetic pathways, arising form the spinal cord and distributing to the midgut via the paravertebral ganglia. Several abnormalities of gut sensori-motor function have been described in patients with IBS. Abnormal motility patterns have been described at the intestinal and colonic levels. Changes in colonic motility are mainly related to bowel disturbances linked to IBS but do not correlate with pain. More recently, visceral hypersensitivity has been recognised as a main characteristic of patients with IBS. It is defined by an exaggerated perception of luminal distension of various segments of the gut and related to peripheral changes in the processing of visceral sensations as well as modulation of perception by centrally acting factors including mood and stress. Viscero-visceral reflexes link the two edges of the brain-gut axis and may account for the origin of symptoms in some pathological conditions. Recent advances in the understanding of the role of myenteric plexus allowed recognition of several neurotransmitters involved at the level of both the afferent and efferent pathways. Targeting the receptors of these neurotransmitters is a promising way for development of new treatments for IBS.     

Visceral afferent hypersensitivity in irritable bowel syndrome—evaluation by cerebral evoked potential after rectal stimulation

OBJECTIVES: Gut hypersensitivity has been shown to be present in irritable bowel syndrome. The current study sought to determine the involvement or hypersensitivity of the gut afferents, objectively, by recording cerebral evoked potential after rectal stimulation. METHODS: In 13 patients with irritable bowel syndrome and nine healthy controls, rectal perception thresholds to electrical stimulation were measured, and cerebral evoked potentials were recorded from 2 cm behind vertex (Cz') after rectal stimulation electrically (frequency 1 Hz, duration 0.5 ms) at an intensity 50% above perception threshold and with filter setting 1-250 Hz. RESULTS: Perception thresholds to rectal electrical stimuli in patients with irritable bowel syndrome were lower than controls (p < 0.05). Rectal stimulation led to recognizable and reproducible cerebral evoked potentials. P1, N1, P2 latencies in patients with irritable bowel syndrome were shorter than that in controls (p < 0.05). P1/N1 amplitude was greater in patients with irritable bowel syndrome than in controls (p < 0.05). CONCLUSIONS: The shorter latency and increased amplitude of cerebral evoked potential after rectal stimulation in patients with irritable bowel syndrome compared to controls provide objective evidence supporting visceral afferent hypersensitivity as the underlying mechanism in irritable bowel syndrome.     

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.     

Pain produced by electric stimulation of the rectum in patients with irritable bowel syndrome: further evidence of visceral hyperalgesia

BACKGROUND: Visceral hyperalgesia is most likely a phenomenon of substantial clinical importance and may also play a role in the pathophysiology of the irritable bowel syndrome (IBS). We investigated the manifestation of visceral hyperalgesia in IBS patients by nociceptive electric stimulation of the rectosigmoid junction and rectum. METHODS: Twelve IBS patients fulfilling the Rome criteria and 9 healthy controls were studied. Visceral single and repeated electric burst stimuli were applied with a bipolar electric stimulator inserted through the sigmoidoscope. The sensation (ST) and pain detection (PDT) thresholds were determined in response to single and repeated stimuli at the rectosigmoid junction, and PDT to repeated stimuli at four different positions in the rectum. Cutaneous single and repeated electric stimuli were applied to the lateral aspect of the foot, determining ST and PDT. RESULTS: Cutaneous stimulation showed no significant differences for ST and PDT between patients and controls. The rectosigmoid junction showed significantly lower ST for single stimuli (P<0.01) and a significantly lower PDT for single and for repeated stimuli (P<0.05 and P<0.02) in IBS patients. In the rectum the IBS patients had a significantly lower PDT than controls (P<0.001). CONCLUSIONS: For cutaneous electric stimulation no differences in the pain thresholds between the two groups were found, showing that there is no generalized hyperalgesia in IBS patients. The IBS patients had a specific decrease of the pain thresholds in the rectum and rectosigmoid junction, indicating visceral hyperalgesia. These results point to central visceral hyperexcitability as an important factor in the pathophysiology of IBS.     

脑源性神经营养因子在乳鼠结肠扩张刺激诱导的慢性内脏高敏感和肠道动力异常中的作用

背景：慢性内脏高敏感和肠道动力异常是肠易激综合征（IBS）的主要病理生理特征，但两者的形成机制至今尚未明确。目的：研究乳鼠结肠扩张刺激动物模型成年后内脏感觉和肠道动力的变化以及脑源性神经营养因子（BDNF）在其中所起的作用，从而探讨BDNF在IBS发病机制中的作用。方法：建立乳鼠结肠扩张动物模型，通过检测成年大鼠对结直肠扩张的行为学反应评估内脏感觉．通过检测全胃肠和小肠传输功能评估肠道动力。比较腹腔注射BDNF抗体后内脏感觉和肠道动力的变化情况。以逆转录聚合酶链反应（RT-PCR）、蛋白质印迹法、酶联免疫吸附测定（EUSA）检测各组回肠、结肠BDNF及其受体TrkB的表达。结果：模型组成年后内脏敏感性增高，肠道动力增强。应用BDNF抗体后模型组内脏敏感性降低，肠道动力减弱。除成年期模型组结肠TrkB mRNA表达外，其余各组BDNF和TrkB mRNA表达均显著高于对照组（P〈0．05）。乳鼠期和成年期模型组回肠、结肠BDNF和TrkB蛋白表达均显著高于对照组（P〈0．05）。结论：BDNF在慢性内脏高敏感和肠道动力的变化中起一定作用，参与了IBS的发生。     

Perception of electrocutaneous stimuli in irritable bowel syndrome

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are common conditions with some similarities, but different perceptual responses to somatic and visceral stimuli. The purpose of this study was to assess in a large group of IBS patients the somatic perception by transcutaneous electrical nerve stimulation (TENS) and its relation to the level of severity and presence of FMS. METHODS: In 99 patients grouped by the validated functional bowel disorder severity index (FBDSI) in mild, moderate, and severe IBS and in 33 healthy controls (HC), we studied discomfort thresholds and perception of somatic stimuli at control (hands and elbows) and active (trapezius) sites by TENS and by using a specific questionnaire. RESULTS: The use of TENS showed that IBS showed significant higher thresholds and lower perception cumulative score compared to HC. The severity of IBS is significantly associated with age and mean control site values for discomfort and borderline associated with gender in the ordinal model constructed for the ascending series protocol. The severity of IBS is also significantly associated with the active cumulative perception score in the long stimulus protocol. Due to limited sample size of IBS men with FMS, analyses of discomfort thresholds and cumulative perception score by FMS were done only for women. IBS women without FMS had significantly higher mean control site values for discomfort and significantly lower active cumulative perception score than HC. IBS women with FMS had significantly lower mean active site values for discomfort thresholds than IBS women without FMS (Dunn's test p < 0.05). CONCLUSIONS: IBS patients showed somatic hypoalgesia to electrical stimuli. The severity of IBS and the presence of FMS influence the perception of somatic stimuli induced by TENS.     

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.     

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