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Background: lBS affects 5-11% of the population of most countries. Prevalence peaks in the third and fourth decades, with a female predominance. Aim: To provide a guide for the assessment and management of adult patients with irritable bowel syndrome. Methods: Members of the Clinical Services Committee of The British Society of Gastroenterology were allocated particular areas to produce review documents. Literature searching included systematic searches using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases and extensive personal reference databases. Results: Patients can usefully be classified by predominant bowel habit. Few investigations are needed except when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse psychological features and somatisation are often present. Ascertaining the patients' concerns and explaining symptoms in simple terms improves outcome. lBS is a heterogeneous condition with a range of treatments, each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; ispaghula improves pain and bowel habit; 5-HT3 antagonists improve global symptoms, diarrhoea, and pain but may rarely cause unexplained colitis; 5-HT4 agonists improve global symptoms, constipation, and bloating; selective serotonin reuptake inhibitors improve global symptoms. Conclusions: Better ways of identifying which patients will respond to specific treatments are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Oesophageal acid infusion induces enhanced pain hypersensitivity in non-acid exposed upper oesophagus (secondary hyperalgesia) in patients with non-cardiac chest pain, thus suggesting central sensitisation contributes to visceral pain hypersensitivity in functional gut disorders (FGD). Perceptual wind-up (increased pain perception to constant intensity sensory stimuli at frequencies ⩾0.3 Hz) is used as a proxy for central sensitisation to investigate pain syndromes where pain hypersensitivity is important (for example, fibromyalgia). Aims: Wind-up in central sensitisation induced human visceral pain hypersensitivity has not been explored. We hypothesised that if wind-up is a proxy for central sensitisation induced human visceral pain hypersensitivity, then oesophageal wind-up should be enhanced by secondary hyperalgesia. Methods: In eight healthy volunteers (seven males; mean age 32 years), perception at pain threshold to a train of 20 electrical stimuli applied to the hand and upper oesophagus (UO) at either 0.1 Hz (control) or 2 Hz was determined before and one hour after a 30 minute lower oesophageal acid infusion. Results: Wind-up occurred only with the 2 Hz train in the UO and hand (both p=0.01 ). Following acid infusion, pain threshold decreased (17 (4)%; p=0.01) in the UO, suggesting the presence of secondary hyperalgesia. Wind-up to the 2 Hz train increased in the UO (wind-up ratio 1.4 (0.1) to 1.6 (0.1); p=0.03) but not in the hand (wind-up ratio 1.3 (0.1) and 1.3 (0.1); p=0.3) Conclusion: Enhanced wind-up after secondary oesophageal hyperalgesia suggests that visceral pain hypersensitivity induced by central sensitisation results from increased central neuronal excitability. Wind-up may offer new opportunities to investigate the contribution of central neuronal changes to symptoms in FGD. [ABSTRACT FROM AUTHOR]

This article focuses on the brain imaging. The two main brain imaging techniques discussed in this article are functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). PET relies on the principle of detecting positron emitting radionuclides that are intravenously injected into a subject positioned so that the head is placed in a specialized detection system. fMRI produces images of active brain regions by detecting indirect effects of neural activity of local blood flow, volume, and oxygen saturation, giving detailed information regarding the functional neuroanatomy of the brain.

Background and aims: This study assessed whether childhood and current adversities: (a) were more prevalent in patients with functional dyspepsia (FD) or non-cardiac chest pain (NCCP) than in patients with gastro-oesophageal reflux disease (GORD) or ischaemic heart disease (IHD); and (b) predicted health related quality of life in these disorders. Patients: Cohort study of consecutive attenders to gastroenterology and cardiology clinics in a secondary tertiary referral centre. Methods: Patients were interviewed using the childhood experience of care and abuse and life events and difficulties schedules. Distress was assessed by questionnaire. Outcome was assessed using SF36 at the index clinic visit and six months later. Results: A total of 133 patients were included (40 NCCP, 43 FD, 29 GORD, and 21 IHD) (67% response rate). The diagnostic groups did not differ significantly in the proportion reporting childhood adversity (30%), ongoing social stress (40%), lack of a close confidant (14%), or level of psychological distress. Reported childhood adversity was associated with poor outcome at the index visit (SF36 physical component score: 36.6 (SEM 1 .8) v 42.3 (SEM 1.2) for the remainder; p = 0.014). In multiple regression analysis, childhood adversity was a significant independent predictor for patients with functional disorders (NCCP and FD) but not organic disorders (GORD or IHD). Change in SF36 score at six months was determined by age and distress score at the index visit in both groups. Conclusion: Childhood adversity was common among this consecutive sample but was associated directly with poor outcome only in patients with functional gastrointestinal syndromes. Distress is an important predictor of outcome in all patients. Greatest impairment occurs when lack of social support accompanies reported childhood adversity. [ABSTRACT FROM AUTHOR]

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 cornices 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. [ABSTRACT FROM AUTHOR]

The article reports on the tutorial entitled "A patient with impaired gastric motility," which was hosted on a learning website for medical professionals from the company BMJ Publishing Group. The tutorial discusses the functional effects of gastrointestinal pathology. The tutorial also informs about the significance of Helicobacter pylori infection in gastric function impairment.

One of the major problems encountered by researchers studying the aetiology of non-cardiac chest pain (NCCP) is the heterogeneity of the group. While visceral hypersensitivity (VH) is thought to be important in the generation of symptoms in NCCP, conventional physiological assessments do not allow one to objectively investigate or differentiate between the potential neurophysiological mechanisms that may cause it. This study aims to explore the neurophysiological basis for VH in NCCP. The potentiation of oesophageal evoked potentials components in group 2 patients indicates enhanced oesophogeal afferent transmission, similar to that seen following the induction of experimental oesophageal sensitisation.

Introduction: Functional Magnetic Resonance Imaging (fMRI) can be used to objectively quantify perception of visceral sensation. However, the neural correlates of varying, quantifiable, intensities of visceral stimulation have remain unclear and the regions involved in encoding of stimulation intensity are not fully understood. Aims: To determine the neural correlates of varying intensities of oesophageal stimulation using fMRI. Methods: 7 healthy volunteers participated in the study. The protocol consisted of four conditions. During each condition one of four balloon distension intensities, obtained by dividing the difference between sensory (0%) and pain thresholds (100%) into 4 levels at 25% increments ie 25%, 50%, 75%, and 100% were used to stimulate the distal oesophagus. A modified bock design was employed where each "active" and "rest" phase was repeated five times. This design was employed four times, once for each intensity. Behavioural data measuring the subjective perception of the stimulus was acquired using visual analogue scales (VAS). Results: VAS scores increased progressively with increasing stimulation intensities (p < 0.001). In response to 100% and 75% stimulation intensity, activation was seen in the anterior cingulate gyrus (ACG) (BA 24 32) bilatera insula suppementary motor cortex (SMA), thalamus primary and secondary sensorory cortices (SI and SII) and dorsolateral' prefrontal cortex (DLPFC). 50% and 25% intensity (non-painful) stimuli activated the same regions to a lesser extent with the exception of the thalamus, and SII, and additional activation in the inferior frontal gyrus. Further analysis revealed that there was a significant trend (p < 0.05) of an increase in cerebral activity with an increase in stimulation intensity, in the ACG (BA24], and SI (bilateral). Conclusions: Visceral stimulation results in a complex pattern of cerebral activation that is similar across varying levels of stimulation intensity. The ACG and SI, both... [ABSTRACT FROM AUTHOR]

Introduction The Joint Hypermobility Syndrome (JHS) is a relatively frequent inherited connective tissue disorder characterised by marked joint hyperextensibility and extra-articular manifestations. Recent work suggests that gastrointestinal (GI) symptom prevalence may be as high as 86% in these patients, and that many of them have evidence of GI dysmotility. Dysphagia is a symptom which is not uncommon in these patients, but which has never been formally studied. In general terms, dysphagia is either due to a structural abnormality of the oesophagus or a motility problem. Methods A single-centre retrospective observational study was carried out to characterise the cause of non-structural dysphagia in patients with JHS. JHS patients who were referred to the upper GI physiology unit and who complained of dysphagia were identified. Their HRM and 24-h pH-metry traces were analysed to characterise oesophageal motility, presence of a hiatus hernia, lower oesophageal sphincter (LOS) pressure and presence of gastro-oesophageal reflux (GOR). Results 17 patients with JHS and dysphagia were referred by the rheumatologists to our unit in 1 year: 76% female; age range: 12–58. None had evidence of a structural cause for the dysphagia on either gastroscopy or barium studies. 10 (59%) had an oesophageal dysmotility to account for their dysphagia – out of these one had achalasia; the other 9 (53%) had oesophageal hypomotility with 7 having frequent hypotensive peristalsis and 2 having intermittent hypotensive peristalsis. 33% of those with hypomotility had a normal Multiple Rapid Swallow test (MRS). 7 of the 17 patients (41%) had normal oesophageal motility and 6 of these had reflux studies: 50% had GOR, 17% had a hypersensitive oesophagus and the remaining 33% had normal studies. Only 2 patients (12%) had hiatus hernias and both of these had oesophageal hypomotility and no GOR. Conclusion This is the first study of upper GI physiology in patients with JHS and non-structural dysphagia. Oesophageal hypomotility is common in these patients and those patients with normal MRS are likely to show the best response to prokinetics. 50% of those with normal motility had pathological GOR and would benefit from high dose proton pump inhibitor therapy. The remainder had normal studies, suggesting hypersensitivity which may respond to treatment with neuromodulators such as amitriptyline. Only 12% of patients had a hiatus hernia, which is in contrast to previous studies. Further prospective studies are required to understand the pathophysiology and management options for dysphagia in JHS. [ABSTRACT FROM PUBLISHER]

Introduction Joint hypermobility (JHM) refers to the hyperextensibility of joints and is common, with a prevalence of 5–17%. It is associated with joint pain but unlike conventional arthropathies, radiological and inflammatory marker abnormalities are absent. JHM tends to be under-diagnosed, even by rheumatologists. Joint pain is common in inflammatory bowel disease (IBD) and is often attributed to seronegative arthropathy. A recent small study suggested that JHM was more common in patients with CD than in UC and healthy controls, and may account for joint pain in these patients. Methods We aimed to assess whether: (1) JHM is more common in patients with IBD than in healthy controls. (2) Joint pain is more common in patients with JHM than without. (3) Patients with JHM and joint pain are misdiagnosed as having arthropathies. In a dual-centre prospective observational study in secondary care, 348 follow-up patients (51% female; age range 16–90) attending IBD clinics were asked to complete a validated 5-point JHM questionnaire, and answer questions related to joint pain, previous diagnoses of arthritis and analgesic use. Patients who scored positive on ≥2 hypermobility questions were considered hypermobile. For patients reporting ‘arthritis', medical records were checked for a rheumatology diagnosis.250 healthy volunteers with no joint pain served as controls. Results 19% patients were hypermobile. There was no difference in the prevalence of JHM in CD (18%) compared to UC (21%) or healthy controls (18%), p=0.49. 56% IBD patients reported joint pain: more patients with JHM (69%) than without (53%, p=0.03) complained of joint pain, but they were less likely to use analgesia (23%) than those without JHM (36%, p<0.05). Of 176 patients reporting joint pain, only 21% had a rheumatological diagnosis of arthropathy and this was similar whether they had (24%) or did not have JHM (20%, p=0.61). Only one patient with joint pain (0.1%) had been diagnosed with hypermobility. Conclusion The prevalence of JHM is not increased in patients with IBD, whether CD or UC. More patients with than without JHM have joint pains but the two groups are equally likely to be diagnosed with arthropathy. Only 1 patient had been diagnosed with hypermobility. Hypermobility seems to be under-diagnosed in patients referred from IBD to rheumatology clinics for assessment of joint pain and should be considered when patients do not clearly satisfy criteria for other arthropathies to ensure they are treated appropriately. [ABSTRACT FROM PUBLISHER]

Introduction Patients with Functional Gastrointestinal Disorders (FGID) often display persistent and heightened pain sensitivity to experimental gut stimulation, a phenomenon known as Visceral Pain Hypersensitivity (VPH). Current management of pain in FGID involves the use of either antispasmodics or antidepressants; both are often unsatisfactory. The role of the autonomic nervous system (ANS) in modulating pain is well known; however, the effect of ANS modulation on VPH has not been studied. Methods The aim was to determine whether physiological modulation of the Autonomic Nervous System (ANS) influences the degree of oeosophageal VPH in healthy volunteers using a validated model.10 healthy volunteers (avr age 30.5 years; 8 male, 6 w-British) underwent psychological profiling for stress, anxiety and personality type. : Pain thresholds to proximal and distal oesophageal electrical stimulation were measured. Thereafter the subjects underwent hydrochloric acid infusion (0.15 M) in the distal oesophagus for 30 min. This was followed by measurements of oesophageal pain threshold (using visual analogue scales) to electrical stimulation in the proximal, unexposed oesophagus at 30, 60 and 90 min. Study 2 was performed at an interval of 2 weeks and the protocol was identical to that of study 1 except that during the acid infusion cardiac vagal tone(CVT) was increased by deep breathing at full inspiratory capacity in 4 sec followed by forced expiratory vital capacity in 6 sec at a frequency of 0.1 Hz (6 breaths/minute, over 5 min). ANS was monitored throughout in both studies. Results The majority of volunteers were ‘agreeable extroverts’, which are protective personality factors. There was only 10% depression and 20% anxiety, showing our exclusion criteria effective. 70% of the subjects rated significant for alexithymia and showed a weak non-significant correlation with the level of sensitisation to acid (r = 0.49 p = 0.14). In study 1 in comparison to baseline, we observed a reduction in CVT during acid exposure while in study 2 the CVT increased during acid exposure, that is, (study 1 difference of -0.09 vs baseline; study 2 difference of 4.93 vs baseline) (p = 0.006). In study 2, all 10 volunteers reduced their level of oesophageal sensitisation to acid in comparison to study 1 with 50% failing to sensitise completely. Overall there was a reduction in sensitisation of 16 mA between study 1 and 2 (p = 0.004). Conclusion This preliminary study suggests that the parasympathetic nervous system has anti-hyperalgesic properties in human oesophageal VPH. This data points to a possible change in the way we treat visceral pain, highlighting likely new targets for the development of novel treatments. Further research is now required with a powered study focusing on exploring mechanism of desensitisation during deep breathing. [ABSTRACT FROM PUBLISHER]

Introduction Females are more likely than males to suffer from many chronic pain conditions, including functional gastrointestinal disorders. However, due to the limited number of studies, information available about gender-differences in normal human central processing of visceral pain is still preliminary. We investigated whether gender differences exist in brain response to visceralpain in a large cohort of healthy volunteers. Methods Sixteen males and sixteen females (mean age = 31 and 28, respectively) participated in the study. Functional magnetic resonance imaging was used to acquire blood oxygen level dependant contrast images at 3 Tesla. Data was collected whilst subjects received painful balloon distensions to the distal esophagus as well as during anticipation of pain. The Eysenck Personality Questionnaire-Revised (EPQ-R) was used to assess personality trait in each subject. During fMRI scanning, subjective perception of the pain stimulus was measured by visual analogue scale, as well as skin conductance response (SCR). Results There was no significant difference in subjective ratings of pain and personality scale (neuroticism, extraversion and psychoticism) between males and females. Males showed higher SCR in anticipation and oesophageal pain compared to rest (p = 0.02, p = 0.0002, respectively). Female showed higher SCR in only pain compared to rest (p = 0.0006). During anticipation, males demonstrated greater activation in the right amygdale and anterior cerebellum, whilst females produced greater brain activity than males in the right supplementary motor area (SMA) and posterior cerebellum. During oesophageal pain males showed greater activation in the SMA and left caudate, whilst females showed greater activation in the mid cingulate cortex, premotor cortex and cerebellum. All brain data was significant at least level p ≤ 0.05. Conclusion Brain activity during anticipation suggests men may experience fear whilst women may mount a planningmotor response. During pain, men show an increased motor response whilst women preferentially activate brain areas associated with the negative affective component of pain suggesting they may attribute more negative emotions during pain processing. These differences may underliethe gender biases that exist in functional pain disorders that are more prevalent in females and where affective comorbidity is present. [ABSTRACT FROM PUBLISHER]

Introduction Immunoreactive nerves and epithelial markers have been studied in the context of acid induced oesophageal hypersensitivity. Increase in immunoreactive TRPV1 nerves are associated with presence of oesophagitis as well as acid exposure time. ASIC3 was identified in epithelium of rat oesophagus and ASIC inhibitor (Amitidine) prevented oesophageal hyperaemic response in rats to CO2 infusion (mimicking acid). We aim to identify ASIC 3 in human oesophageal epithelium and to determine if it is a suitable biomarker of symptom severity in patients with gastro-oesophageal reflux disease (GORD). Methods 36 oesophageal mucosal biopsy samples from patients (age 19–59 years and 17 females) with or without GORD undergoing gastroscopy were obtained and their clinical symptoms were assessed using visual analogue scale (VAS) adapted from validated questionnaire ReQUEST. The symptoms assessed were; general feeling, acid complaints, upper abdominal complaints, lower abdominal complaints, nausea, sleep disturbances. Samples were paraffin fixed and analysed using immunohistochemistry for PGP 9.5 and ASIC3. Results Epithelial ASIC3 was identified in the mucosal biopsies (14 controls, 18 non-erosive reflux disease, 4 erosive oesophagitis). ASIC3 could be classified based on distribution and morphology into 4 groups; basal layer (stratum basale), stratum spinosum perinuclear, stratum spinosum membrane bound and superficial luminal layer staining. Patients who scored higher on VAS for all 6 symptoms also demonstrated higher expression of all 4 ASIC3 features studied (median 65% (35–87) vs 57% (34–79), p=0.018). In particular, for acid complaints, sleep disturbance and lower GI complaints, this association was more significant (median 64% (46–81) vs 54% (38–69), p=0.002). Nerve fibres as stained by PGP 9.5 in human oesophageal epithelium were absent. Conclusion Presence of specific epithelial ASIC3 features in oesophageal epithelium was associated with increase in severity of common GORD symptoms. Further quantitative studies are required to study correlation of ASIC3 as an objective biomarker of symptom severity. [ABSTRACT FROM PUBLISHER]

Introduction The lack of objective biomarkers to assess nausea and susceptibility in humans makes clinical decisions difficult. Furthermore, animal studies unable to identify nausea well is potentially an animal welfare issue. We aim to study the psychophysiological and brain processing response to a novel method of nausea induction. Methods 10-min video inducing motion sickness and control were used (51 healthy volunteers; age 27 ± 8 years, 22 male) with tests of motion sickness and psychological questionnaires; cardiac sympathetic (cardiac sympathetic index CSI, heart rate HR, mean blood pressure MBP) and parasympathetic (cardiac vagal tone CVT, cardiac sensitivity to baroreceptor reflex CSB) measures; cortisol levels and electrogastrogram (EGG). 9 susceptible subjects had same stimuli again (age 25 ± 5 years, 5 male) with functional MRI analysed with XBAM. Results All subjects completed without vomiting. Comparing nausea video (NA) to control, NA increased nausea (nausea VAS +57%±11, p<0.01). Furthermore, NA raised sympathetic (HR +4.04±0.94, p<0.01; SBP +2.4±1.75, p=0.18; DBP +2.23±0.98, p<0.05; MBP +2.28±1.12, p<0.05) and lowered parasympathetic activity (CVT −1.36±0.49, p<0.01; CSB −1.27±0.61, p<0.05); raised dominant frequency (EGG 3.0±0.04 vs 2.8±0.05, p<0.02). Comparing nausea susceptible versus resistant, moderate to severe nausea lowered CVT and CSB; raised HR; raised cortisol; reduced EGG dominant power (% change from baseline −20.6±7.7 vs −11.2±0.8, p<0.01; −25.1±9.4 vs 8.2±10.7, p<0.05; 10.4±3.4 vs 0.8±2.2, p<0.05; 16.9±20.2 vs −28.5±4.9, p<0.05; −2.81±1.36 vs −0.17±0.93, p<0.01, respectively). 9 susceptible subjects (fMRI) comparing nausea video to control, show correlations to nausea levels with raised brain activity in the inferior frontal gyrus (p<0.01) and temporal lobe (p<0.01) and reduced brain activity in multiple areas of the occipital lobe (p<0.01) and cerebellum (p<0.05). Conclusion This model is safe and effective. Nausea susceptible subjects show lowered CVT and CSB; raised HR; raised cortisol; reduced dominant power on EGG from baseline compared to resistant subjects. Nausea susceptible show different brain processing patterns in the NA compared to control. These biomarkers can then be used for reverse translation in animals to potentially improve animal models as well as reduce animal suffering from undetected nausea. [ABSTRACT FROM PUBLISHER]

Introduction Functional chest pain of presumed oesophageal origin (FCP) is a complex disorder whose pathophysiology is incompletely understood. In a previous study we have demonstrated the existence of two reproducible human pain endophenotypes based on personality, serotonin transporter genotype (5-HTTLPR), autonomic (ANS) and cortisol responses to pain. The aim of this study was to evaluate the clinical salience of these endophenotypes in patients with FCP. Methods 20 patients with FCP (9 male, mean age 38.7 years, range 21–59 years) and 20 healthy age, sex, ethnicity matched volunteers (9 male, mean 38.2 years, range 22–49) had personality traits assessed using validated questionnaires. Subjects had validated ANS parameters measured at baseline and continuously thereafter. Following baseline recordings, venous blood was taken for cortisol and 5-HTTLPR genotyping. Subjects received 7 somatic stimuli (nail bed pressure) followed by 7 visceral stimuli (oesophageal balloon distension) to pain tolerance. Blood was further sampled for serum cortisol after somatic and visceral pain. Results Patients had higher neuroticism, state and trait anxiety and depression scores but lower extroversion scores versus controls (all p<0.005). Patients tolerated less quantity of somatic and visceral stimulus versus controls (48.4 N vs 70.6 N, p<0.0001 and 30 ml vs 50.9 ml, p=0.009 respectively). Cluster analysis, demonstrated the presence of 2 clusters or endophenotypes. One endophenotype had higher neuroticism scores (p<0.0001), had the short () allele of the 5-HTTLPR (p<0.001), had higher baseline cortisol (p=0.001), had higher anxiety (p=0.002), higher sympathetic tone at rest (p=0.001) and increased their parasympathetic tone to pain (p=0.001 and p=0.002 respectively). The second endophenotype had higher extroversion scores with the converse psychophysiological profile in the absence of the allele. Patients with FCP were over-represented in endophenotype 1, (p=0.01). Conclusion These results provide further evidence for the existence of 2 human pain endophenotypes and that patients with FCP may have a distinct phenotype contributing to its pathophysiology. These findings warrant further investigation to determine if the endophenotype identified in our study is a risk factor for the development of chronic pain such as that observed in other functional gastrointestinal disorders. [ABSTRACT FROM PUBLISHER]

Introduction: The cerebral activation during functional magnetic resonance imaging (fMRI) sessions can be influenced by many variables including scanner noise, subject movement, and cognition, such as habituation and learning. Although the cerebral processing of visceral sensation has been studied, information regarding the trial re-trail reliability is not available. Aims: The purpose of this study was to assess the reproducibility of the functional neural correlates of oesophageal sensation, using fMRI. Methods: 7 healthy volunteers participated in the studv. The protocol consisted of two conditions; non-painful (50% of the difference between sensory and pain thresholds) and painful (pain threshold) stimulation intensities using phasic balloon distension in the distal oesophagus. The order of presentation of these intensities was counterbalanced. A mod fled block design was employed for each intensity where "active" and "rest" phases were repeated five times. This experimental procedure was repeated on two additional occasions (three scans in total) to investigate the consistency of cerebral activation over time. Results: In response to painful stimulation highly reproducible activation was seen in the anterior cingulate gyrus (ACG) (BA24, 32), bilateral insula, supplementary motor cortex (SMA), thalamus, primary and secondary sensory cortices (SI&SII) and dorsolateral prefrontal cortex. Further analysis revealed a significant (p < 0.05) decrease in cerebral activity from the first to the final scan in the interior cingulate (ACG), SMA and SI. Activation in response to non-painful stimulation was seen in similar regions to those seen during painful stimulation. with the exception of the thalamus, but was found to be more variable in the ACC, SI, SII, and SMA in comparison to painful stimulation. Conclusions: Painful stimulation of the oesophagus produces robust activity in many brain regions previously associated with visceral pain. Non-painful... [ABSTRACT FROM AUTHOR]

Introduction: Recent studies indicate that proximal oesophageal (PO) pain hypersensitivity to distal oesophageal acid infusion occurs due to increased neuronal excitability, ie central sensitisation CS. In somatic tissues the induction of CS in the spinal cord is dependent on the N-methyI-D-aspartate (NMDA) receptor, however, the role of the NMDA receptor in mediating visceral hypersensitivity is unknown. Aim: To determine if the NMDA receptor antagonist ketamine attenuates CS in a model of human oesophageal hypersensitivity. Methods: 14 healthy subjects (7 male, age 18-43 years) were studied in a randomised two way double blind placebo controlled crossover study. Pain thresholds (PT) to electrical stimulation were determined in the PO and foot, and then either ketamine (0.075 mg/kg) or placebo (0.9% NaCI) was given as an intravenous bolus. A 30 min infusion of 0.15 M acid was then given in the distal oesophagus together with an intravenous infusion of ketamine 0.005 mg/kg) or placebo (0.9% NaCI) for 30 min. PT in the PO and foot were then repeatedly tested for 120 min post-infusion. PO pH and an attention task was performed throughout. Results: In all but one subject (excluded from analysis) the pH remained above 5 in the PO during each study. Ketamine attenuated the reduction in PT in the PO in response to acid in the distal oesophagus (Area under curve (AUC+ 16.9±3.9 and 12.3±2.6 for ketamine and placebo, respectively, p < 0.002). Ketamine did not affect PT in the foot compared with placebo (AUC 10.8±4.7 and 11.2±5.2, p = 0.5). Ketamine reduced attention scores during the infusion compared with baseline (Mean 54.4±2.6 and 46.1±4.6, respectively, p < 0.001) but this had ceased 30 min post-infusion (mean 54.9±2.8 and 54.4±2.6, p = 0.27). Conclusion: The attenuation of PO hypersensitivity by ketamine suggests that the NMDA receptor contributes to the generation of CS in visceral pain. Therefore, NMDA... [ABSTRACT FROM AUTHOR]