Cognitive modulation of the cerebral processing of human oesophageal sensation using functional magnetic resonance imaging

BACKGROUND: While cortical processing of visceral sensation has been described, the role that cognitive factors play in modulating this processing remains unclear. AIM: To investigate how selective and divided attention modulate the cerebral processing of oesophageal sensation. METHODS: In seven healthy volunteers (six males, mean age 33 years; ranging from 24 to 41 years old) from the general community, phasic visual and oesophageal (non-painful balloon distension) stimuli were presented simultaneously. During the selective attention task, subjects were instructed to press a button either to a change in frequency of oesophageal or visual stimuli. During a divided attention task, subjects received simultaneous visual and oesophageal stimuli and were instructed to press a button in response to a change in frequency of both stimuli. RESULTS: Selectively focussing attention on oesophageal stimuli activated the visceral sensory and cognitive neural networks (primary and secondary sensory cortices and anterior cingulate cortex respectively) while selective attention to visual stimuli primarily activated the visual cortex. When attention was divided between the two sensory modalities, more brain regions in the sensory and cognitive domains were utilised to process oesophageal stimuli in comparison to those employed to process visual stimuli (p=0.003). CONCLUSION: Selective and divided attention to visceral stimuli recruits more neural resources in both the sensory and cognitive domains than attention to visual stimuli. We provide neurobiological evidence that demonstrates the biological importance placed on visceral sensations and demonstrate the influence of cognitive factors such as attention on the cerebral processing of visceral sensation.     

Neurophysiology of gastrointestinal pain

The only non-general sensation that can be evoked from the gastrointestinal (GI) tract is that of pain ranging from mild discomfort to intense pain. However, in certain regions of the gut, such as the rectum and gastro-oesophagus, the feeling of pain can be preceded by non-painful sensations of distension at lower stimulus intensities. GI pain is often dull, aching, ill-defined and badly localized. In some cases, GI pain is projected to areas of the body away from the originating viscus ('referred' pain). These properties indicate that the representation of internal organs within the central nervous system is very imprecise. Behavioural, neurophysiological and clinical evidence shows that most forms of GI pain are mediated by activity in visceral afferent fibres running in sympathetic nerves and that the afferent innervation of the gut mediated by parasympathetic nerves is not primarily concerned with the signalling and transmission of GI pain. As for the encoding mechanism of the peripheral sensory receptor in the gut, there is evidence for the existence of specific visceral nociceptors in some locations (e.g. the biliary system) and for the existence of non-specific 'intensity' type receptors in other locations (e.g. the colon). In any case, the actual number of nociceptive afferent fibres in the gut is very small and this explains why large areas of the GI tract appear to be insensitive or require considerable stimulation before giving rise to painful sensations. The few nociceptive afferents contained in sympathetic nerves can excite many second order neurones in the spinal cord which in turn generate extensive divergence within the spinal cord and brain stem, sometimes involving long supraspinal loops. Such a divergent input can activate many different systems, motor and autonomic as well as sensory, and thus trigger the general reactions that are characteristic of visceral nociception: a diffuse and ill-localized pain sometimes referred to somatic areas, and autonomic and somatic reflexes that result in prolonged motor activity.     

Neurophysiology of gastrointestinal pain

The only non-general sensation that can be elicited from the gastrointestinal (GI) tract is that of pain, which can go from slight discomfort to severe pain. However, in certain parts of the intestine, such as the rectum and gastroesophagus, the sensation of pain can be preceded by a non-painful sensation of distension at low levels of stimulation. GI pain is often dull, poorly defined and difficult to pinpoint. In some cases, GI pain is projected to areas of the body distant from the source organ ("referred" pain). These characteristics indicate that the representation of internal organs within the nervous system is very imprecise. Experimental evidence based on behavioral, neurological and clinical testing shows that most GI pain is the result of activity in afferent visceral sensory fibers contained in sympathetic nerves, and that the afferent intestinal innervation by means of parasympathetic nerves is not essentially related to GI pain signalling and transmission. As for the peripheral sensory receptor coding mechanism in the intestine, experimental tests have shown the existence of specific visceral nociceptors in certain places (e.g., the biliary system) and the existence of a king of non-specific "intensity" receptors in others (e.g. the colon). In any case, the number of afferent nociceptive fibers in the intestine is minimal, and this accounts for the fact that large areas of the GI tract appear to be insensitive or to require considerable stimulation before pain can be elicited. The few afferent nociceptive fibers contained in the sympathetic nerves can excite quite a few second order neurons in the medulla spinalis, which in turn generate an extensive divergence within the medulla spinalis and brain stem, including at times long supraspinal branches. This divergent input can activate different motor, autonomous and sensory systems, thus triggering the general reactions which characterize visceral nociception: diffuse pain which is difficult to pinpoint, referred at times to somatic areas, and autonomous and somatic reflexes resulting in prolonged motor activity.     

应用功能性磁共振成像技术研究非糜烂性反流病患者食管酸灌注时大脑功能活动模式的变化

背景：血氧水平依赖性功能性磁共振成像（BOLD-fMRI）技术近来被广泛应用于人体内脏感觉的研究，而非糜烂性反流病（NERD）的发生与内脏感觉高敏有密切关系。目的：应用BOLD-fmRI技术，通过研究食管酸灌注时NERD患者大脑功能活动模式的改变，探讨NERD患者食管内脏高敏感的中枢机制。方法：对31例NERD、13例反流性食管炎（RE）和12名健康志愿者在食管酸灌注时行fMRI；根据食管内球囊扩张和酸灌注试验结果将NERD患者分为两组：感觉高敏（NERD-H）组和感觉正常（NERD-N）组；对三组受试者大脑的兴奋情况进行统计学分析。结果：食管酸灌注刺激在NERD内脏高敏的患者中激活范围较广泛，包括单侧或双侧第Ⅱ躯体感觉皮质（SⅡ）、第Ⅰ躯体感觉皮质（SI）、前额叶皮质（右侧为主）、眶额回皮质、岛叶皮质、运动区、辅助运动区、前扣带回、后扣带回、楔前叶、杏仁体、腹侧纹状体、丘脑、小脑等，其中双侧SⅡ、右前额叶皮质、运动区、辅助运动区、岛叶皮质、杏仁体、腹侧纹状体和小脑的最大信号增加幅度显著高于NERD-N组和对照组（P〈0．01）。内脏高敏的NERD患者fMRI功能初始信号呈现时间、达峰值时间较NERD-N组和对照组显著缩短（P〈0．01）。结论：食管酸灌注时产生的fMRI参数改变为揭示NERD患者中枢神经系统整合、处理食管感觉传入信息功能异常提供了依据。     

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.     

Brain Responses to Visceral and Somatic Stimuli in Irritable Bowel Syndrome: a Central Nervous System Disorder?

In healthy subjects, the brain regions most consistently activated in visceral and somatic pain are the key regions in the central pain matrix,including the mid/anterior insula, subregions of the ACC, PFC, thalamus,and in some cases, pontine regions such as the dorsal pons and PAG. Functional neuroimaging studies have demonstrated evidence of altered regional brain activation responses during visceral and somatic stimuli in IBS that have been associated with perceptual differences. Although perceptual studies have shown increased sensitivity to rectosigmoid distension in IBS, most somatic pain studies have demonstrated normal or decreased sensitivity compared with controls; however, a recent study showed increased sensitivity to thermal heat. Altered brain responses in IBS,particularly to visceral stimuli, include activation of regions concerned with attentional processes and response selection, corticolimbic regions concerned with emotional and autonomic responses to stimuli, and subcortical regions receiving cortical projections from the latter and afferent input from the soma and viscera. Altered activations of these regions also may be present in the absence of a noxious visceral stimulus. Changes in rCBF of some of these regions have been associated with treatment response in IBS.With regard to differences in cortical processing of visceral versus somatic stimuli in IBS, there have been only two studies. Greater activations of the dorsal ACC, thalamus, and PFC have been shown with visceral stimuli compared with somatic stimuli in IBS. A plausible hypothesis for the observations from brain imaging studies is that IBS patients demonstrate a compromised activation of pain inhibition circuits including those of the cortico-pontine circuit but increased activation of limbic and paralimbic circuits that may be related to pain facilitation.     

Brain response to visceral aversive conditioning: a functional magnetic resonance imaging study

BACKGROUND & AIMS: Brain-imaging studies to date have confounded visceral pain perception with anticipation. We used functional magnetic resonance imaging of the human brain to study the neuroanatomic network involved in aversive conditioning of visceral pain and, thus, anticipation. METHODS: Eight healthy volunteers (5 male) participated in the study. We used a classic conditioning paradigm in which 3 neutral stimuli (differently colored circles) that acted as conditioned stimuli were paired with painful esophageal distention, air puff to the wrist, or nothing, which acted as unconditioned stimuli. Neural activity was measured during learning, anticipation (pairing only 50% of conditioned stimuli with their unconditioned stimuli), and extinction (unpaired conditioned stimuli) phases. For magnetic resonance imaging, axial slices depicting blood oxygen level-dependent contrast were acquired with a 1.5-T system. RESULTS: Neural responses during the learning phase included areas commonly associated with visceral pain (anterior cingulate cortex, insula, and primary and secondary somatosensory cortices) and innocuous somatosensory perception (primary and secondary somatosensory cortices and insula). During the anticipation and extinction phases of aversive stimulation, brain activity resembled that seen during actual painful esophageal stimulation. In contrast, anticipation and extinction of the innocuous somatic stimulus failed to show that effect. CONCLUSIONS: We have shown that actual and anticipated visceral pain elicit similar cortical responses. These results have implications for the design and interpretation of brain-imaging studies of visceral pain. They not only contribute to our understanding of the processing of visceral pain, but also have clinical implications for the management of chronic pain states.     

Functional brain imaging of gastrointestinal sensation in health and disease

It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitive- exert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested, mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear, mainly due to a lack of non-invasive methods to study the （neurobiological） mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly, has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective ＆ cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut （brain- gut axis） will be briefly outlined, including brain imaging evidence in healthy volunteers. Second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail. Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.     

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.     

Role of stress in functional gastrointestinal disorders. Evidence for stress-induced alterations in gastrointestinal motility and sensitivity.

Psychological stress is widely believed to play a major role in functional gastrointestinal (GI) disorders, especially irritable bowel syndrome (IBS), by precipitating exacerbation of symptoms. The available data clearly demonstrate that inhibition of gastric emptying and stimulation of colonic transit is the most consistent pattern in the motility response of the GI tract to acute or short-term stress. Thus, one might propose that these alterations might play a pathophysiological role in dyspeptic symptoms and alterations in stool frequency and consistency in patients with stress-related functional GI disorders. Taken together, the above-mentioned studies suggest that the colonic motor response to stress is exaggerated in IBS. There is evidence that an increased emotional response is associated with this difference in colonic, and perhaps also gastric motor responses to certain stressors. However, almost no valid data are available so far from human studies addressing the question if differences in motility responses to stress between patients with functional GI disorders and healthy subjects are due to an altered stress response associated with an imbalance of the autonomic nervous system or increased stress susceptibility. We can summarize that in experimental animals the most consistent pattern of GI motor alterations induced by various psychological and physical stressors is that of delaying gastric emptying and accelerating colonic transit. Endogenous corticotropin-releasing factor (CRF) in the brain plays a significant role in the central nervous system mediation of stress-induced inhibition of upper GI and stimulation of lower GI motor function through activation of brain CRF receptors. The inhibition of gastric emptying by CRF may be mediated by interaction with the CRF-2 receptor, while CRF-1 receptors are involved in the colonic and anxiogenic responses to stress. Endogenous serotonin, peripherally released in response to stress, seems to be involved in stress- and central CRF-induced stimulation of colonic motility by acting on 5HT-3 receptors. Taken together, the limited data available from investigations in healthy subjects and patients with functional GI disorders provide some evidence that stress affects visceral sensitivity in humans. Acute psychological stress seems to facilitate increased sensitivity to experimental visceral stimuli, if the stressor induces a significant emotional change. In summary, studies in experimental animals suggest that stress-induced visceral hypersensitivity is centrally mediated by endogenous CRF and involvement of structures of the emotional motor system, e.g. the amygdala. Stress-induced activation or sensitization of mucosal mast cells in the GI tract seem to be involved in stress-associated alterations of visceral sensitivity.     

Ultrasonographic study of mechanosensory properties in human esophagus during mechanical distension

AIM: To study the esophageal geometry and mechano-sensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODS: Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale (VAS). The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAS levels. Distensions were done before and during administration of the anti-cholinergic drug butylscopolamine. RESULTS: The stimulus-response (volume-VAS) curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains. CONCLUSION: The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mech-anosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors.     

Gender-related differences in IBS symptoms

OBJECTIVE: Women are more likely than men to report irritable bowel syndrome (IBS) symptoms as well as chronic visceral and musculoskeletal pain. The study tests the general hypothesis that female IBS patients differ from their male counterparts in symptoms related to the viscera and musculoskeletal system, and that these differences are related to the menstrual cycle. METHODS: Seven hundred fourteen Rome positive IBS patients were evaluated for GI and extracolonic symptoms, psychological symptoms (SCL-90R), and quality of life (QOL) (SF-36). In addition, 54 postmenopausal women were compared with 61 premenopausal women and 54 age-matched males, all with IBS. RESULTS: Male and female subjects reported similar GI levels of symptom severity and psychological problems. Abdominal distension associated with a sensation of bloating was more commonly reported by female patients, as were symptoms of constipation. Female patients more often reported nausea, alterations of taste and smell, and unpleasant sensations on the tongue, muscle stiffness in the morning, greater food sensitivity, and side effects from medications. Forty percent of female patients reported menstrual cycle-related worsening of symptoms, but few symptom differences were found between pre- and postmenopausal women, making it unlikely that most of the gender differences observed are directly tied to the menstrual cycle. CONCLUSIONS: Female patients report higher levels of a variety of intestinal and nonintestinal sensory symptoms despite similar levels of IBS severity, abdominal pain, psychological symptoms, and illness impact. The apparent differences in sensitivity to nonpainful visceral sensations, medications, and food may represent altered sensory processes, autonomic responses, and/or cognitive hypervigilance.     

Hyperglycemia-Induced Attenuation of Rectal Perception Depends upon Pattern of Rectal Balloon Inflation

This study investigated the effects of acutehyperglycemia on conscious rectal perception in responseto two different rectal distension paradigms. Elevenhealthy males were studied in random order on two separate days during euglycemia andhyperglycemia with blood glucose concentrations clampedto 3.8 ± 0.6 and 14.8 ± 0.86 mmol/liter,respectively. In order to evoke sensory responses, rapidphasic and ramplike distensions were applied to anintrarectal balloon. Rectal sensation thresholds forinitial sensation, sensation of stool and discomfort,and sensory intensities were recorded. Additionally,anorectal motor responses were investigated during phasicdistension. Acute hyperglycemia did not modify rectalsensory pressure thresholds and perception scores inresponse to phasic distension. Neither did hyperglycemia alter the resting anal sphincter pressure, thepressure threshold for eliciting the rectoanalinhibitory reflex, or the maximal anal squeeze pressure.In contrast, hyperglycemia attenuated rectal perception in response to ramplike distension. Thepressure thresholds, 10.0 ± 1.8 and 17.0 ±3.6 mm Hg for initial sensation and discomfort,respectively, during hyperglycemia were significantlyhigher than the corresponding thresholds of 4.4 ± 1.4and 11.4 ± 1.9 mm Hg observed during euglycemia(P < 0.01). Higher rectal pressures were observed atall intensities of sensation of stool and discomfortduring hyperglycemia than those obtained duringeuglycemia (P < 0.01). Hyperglycemia did not alterthe compliance of the rectum. The results of this studydemonstrate that acute hyperglycemia attenuates rectal perception, and this attenuation depends uponthe type of distension employed. Our findings alsodemonstrate that anal sphincter motor function is notappreciably modified by hyperglycemia.     

Functional brain imaging in irritable bowel syndrome with rectal balloon－distention by using fMRI

AIM: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity is a key factor in the pathophysiology of IBS. The aim of this study was to examine the effect of rectal balloon-distention stimulus by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the distribution, extent, and intensity of activated areas between IBS patients and normal controls. METHODS: Twenty-six patients with IBS and eleven normal controls were tested for rectal sensation, and the subjective pain intensity at 90 ml and 120 ml rectal balloon-distention was reported by using Visual Analogue Scale. Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon-distention in all subjects. RESULTS: Rectal distention stimulation increased the activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon-distention, the activation area and percentage change in MR signal intensity of the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in patients with IBS than that in controls. Score of pain sensation at 90 ml and 120 ml rectal balloon-distention was significantly higher in patients with IBS than that in controls. CONCLUSION: Using fMRI, some patients with IBS can be detected having visceral hypersensitivity in response to painful rectal balloon-distention. fMRI is an objective brain imaging technique to measure the change in regional cerebral activation more precisely. In this study, IC and PFC of the IBS patients were the major loci of the CNS processing of visceral perception.     

Pathophysiology of functional dyspepsia

Functional dyspepsia is a symptom complex characterised by postprandial upper abdominal discomfort or pain, early satiety, nausea, vomiting, abdominal distension, bloating, and anorexia in the absence of organic disease. Gastrointestinal motor abnormalities, altered visceral sensation, and psychosocial factors have all been identified as major pathophysiological mechanisms. This perspective has now replaced the earlier view that the condition was the result of a sole motor or sensory disorder of the stomach. Future therapeutic strategies should be aimed at reducing nociception as well as enhancing the accommodation response.     

Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, possibly related to abnormal brain-gut communication. Positron emission tomography imaging has suggested specific central nervous system (CNS) abnormalities in visceral pain processing in IBS. This study aimed to determine (1) if functional magnetic resonance imaging (fMRI) detects CNS activity during painful and nonpainful visceral stimulation; and (2) if CNS pain centers in IBS respond abnormally. METHODS: fMRI was performed during nonpainful and painful rectal distention in 18 patients with IBS and 16 controls. RESULTS: Rectal stimulation increased the activity of anterior cingulate (33/34), prefrontal (32/34), insular cortices (33/34), and thalamus (32/34) in most subjects. In IBS subjects, but not controls, pain led to greater activation of the anterior cingulate cortex (ACC) than did nonpainful stimuli. IBS patients had a greater number of pixels activated in the ACC and reported greater intensity of pain at 55-mm Hg distention than controls. CONCLUSIONS: IBS patients activate the ACC, a critical CNS pain center, to a greater extent than controls in response to a painful rectal stimulus. Contrary to previous reports, these data suggest heightened pain sensitivity of the brain-gut axis in IBS, with a normal pattern of activation.     

Abnormal visceral autonomic innervation in neurogenic faecal incontinence.

Changes of denervation in the anal sphincter striated and smooth muscle in patients with neurogenic faecal incontinence are well established. This study aimed to determine if there is also a more proximal visceral autonomic abnormality. Thirty women with purely neurogenic faecal incontinence (prolonged pudendal nerve latencies and an intact sphincter ring) and 12 patients with neuropathic changes together with an anatomical disruption were studied. Two control groups consisted of 18 healthy volunteer women and 17 women with normal innervation but an anatomically disrupted sphincter. Rectal sensation was assessed using balloon distension and electrical mucosal stimulation, and anal sensation by electrical stimulation. Rectal compliance was studied to determine whether sensory changes were primary or caused by altered rectal wall viscoelastic properties. Anal canal pressure changes in response to both rectal distension and rectal electrical stimulation were measured to assess the intrinsic innervation of the internal anal sphincter. Patients with neurogenic incontinence alone had impaired rectal sensation to distension (53.1 v 31.5 ml, p < 0.05, neurogenic v controls) and to electrical stimulation (24.4 v 14.8 mA, p < 0.005). Patients with neurogenic incontinence and sphincter disruption also showed impaired sensation compared with healthy controls (55.8 ml v 31.5 ml, p < 0.05 and 22.9 mA v 14.8 mA, p < 0.05). Patients with only a disrupted sphincter had normal visceral sensation to both types of testing. Both rectal compliance and the response of the internal anal sphincter to rectal distension and electrical stimulation were normal in all patient groups. This study suggests that there is a visceral sensory abnormality in patients with neurogenic incontinence which is not caused by altered rectal compliance. As evaluated in this study the intrinsic innervation of the internal anal sphincter is not affected in this process.     

Sensation of bloating and visible abdominal distension in patients with irritable bowel syndrome

OBJECTIVES: Abdominal bloating and distension are common symptoms of irritable bowel syndrome (IBS). The postulated pathophysiological mechanisms underlying these symptoms include increased production, retention, or perception of gas or luminal contents. The aims of this study were to prospectively compare the prevalence of, and clinical factors related to, bloating and distension in an IBS patient population. METHODS: A total of 714 consecutive patients who met Rome I criteria for IBS were prospectively surveyed, and were classified as having bloating alone (B) or bloating and distension (B+D) based on a comprehensive bowel symptom questionnaire. GI, extraintestinal, and psychological symptoms, as well as health-related quality of life measures were also assessed using validated survey instruments. RESULTS: A total of 542 IBS patients (76%) who reported abdominal bloating were studied. Of these, 132 patients fulfilled criteria for the B group, whereas 410 patients fulfilled criteria for the B+D group. There was a significantly different gender distribution in the B and B+D groups (female:male ratios, 1.4:1 and 2.8:1, respectively p < 0.02). There was also a significantly different bowel habit subgroup distribution, with a greater predominance of constipation in B+D group and of diarrhea in the B group (p < 0.03). Both groups were similar in other clinical parameters, including progressive worsening of symptoms during the day, and relief by passing stool or gas. Both bloating and distension worsened when other abdominal symptoms worsened. Abdominal distension was associated with greater symptom severity and less diurnal variation in symptoms, and was less often perceived as associated with food intake. CONCLUSIONS: Bloating and visible abdominal distension may arise from two distinct but interrelated physiological processes. Although the sensation of bloating may be related to enhanced sensitivity to visceral afferent stimulation, abdominal distension in more severely affected patients may be related to triggering of a visceromotor reflex affecting the tone of abdominal wall muscles.     

Regional cerebral blood flow during gastric balloon distention in functional dyspepsia

BACKGROUND & AIMS: Hypersensitivity to proximal gastric distention as a result of abnormal central nervous system processing of visceral stimuli is a possible pathophysiologic mechanism in functional dyspepsia (FD). Increasing evidence suggests involvement of both lateral and medial pain systems in normal visceral sensitivity and aberrant brain activation patterns in visceral hypersensitivity. We hypothesized that there is involvement of aberrant brain activation in FD with hypersensitivity to gastric distention. Our aim was to investigate regional cerebral blood flow during painful proximal gastric distention in hypersensitive FD. METHODS: Brain (15)O-water positron emission tomography was performed in 13 FD patients with symptoms of gastric hypersensitivity during 3 conditions: no distention, sham distention, and isobaric distention to unpleasant or painful sensation. Pain, discomfort, nausea, and bloating during maximal distention were rated on visual analogue scales. Data were analyzed using statistical parametric mapping. RESULTS: The threshold for painful distention was 6.6 +/- 3.8 mm Hg greater than the minimal distending pressure. At the corrected P level of less than .05, subtraction analysis (painful distention - no distention) showed activations in bilateral gyrus precentralis, bilateral gyrus frontalis inferior, bilateral gyrus frontalis medialis, bilateral gyrus temporalis superior, bilateral cerebellar hemisphere, and left gyrus temporalis inferior. Sham distention minus no distention showed no activations. CONCLUSIONS: Similar to healthy volunteers, proximal stomach distention in FD activates components of the lateral pain system and bilateral frontal inferior gyri, putatively involved in regulation of hunger and satiety. In hypersensitive FD, these activations occur at significantly lower distention pressures. In contrast to findings in normosensitivity, none of the components of the medial pain system were significantly activated.     

Motor responses of the small intestine to intraluminal distension in normal volunteers and a patient with visceral neuropathy.

The motor responses of the small intestine to intraluminal distension were studied proximal and distal to an inflatable balloon in 13 normal volunteers. During fasting, distension rapidly induced a persistent localised inhibition of distal contractile activity with a small proximal increase. Proximally, phase III activity was unaffected during distension but its propagation across and appearance below the balloon was inhibited. Upon deflating the balloon a normal motor pattern rapidly returned. Similar changes were observed during distension in the fed state. The changes in the motor pattern resemble those of the intrinsically mediated 'peristaltic reflex', studied in animals, and suggest that in man the response to balloon distension may also be mediated through an intrinsic mechanism. A patient with a visceral neuropathy, studied in a similar manner, had no inhibition of distal motor activity during distension, suggesting a functional defect of the enteric nerves. Further observations of the motor responses to distension in similar patients seem indicated to determine the usefulness of this technique for evaluating enteric nervous system function when an abnormality is suspected.