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Visceral Hypersensitivity (visceral + hypersensitivity)
Selected AbstractsVisceral perception thresholds after rectal thermal and pressure stimuli in irritable bowel syndrome patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2004YANQING LI Abstract 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. [source] Neuronal correlates of gastric pain induced by fundus distension: a 3T-fMRI studyNEUROGASTROENTEROLOGY & MOTILITY, Issue 5 2004C.-L. Lu Abstract Visceral hypersensitivity in gastric fundus is a possible pathogenesis for functional dyspepsia. The cortical representation of gastric fundus is still unclear. Growing evidence shows that the insula, but not the primary or secondary somatosensory region (SI or SII), may be the cortical target for visceral pain. Animal studies have also demonstrated that amygdala plays an important role in processing visceral pain. We used fMRI to study central projection of stomach pain from fundus balloon distension. We also tested the hypothesis that there will be neither S1 nor S2 activation, but amygdala activation with the fundus distension. A 3T-fMRI was performed on 10 healthy subjects during baseline, fullness (12.7 ± 0.6 mmHg) and moderate gastric pain (17.0 ± 0.8 mmHg). fMRI signal was modelled by convolving the predetermined psychophysical response. Statistical comparisons were performed between conditions on a group level. Gastric pain activated a wide range of cortical and subcortical structures, including thalamus and insula, anterior and posterior cingulate cortices, basal ganglia, caudate nuclei, amygdala, brain stem, cerebellum and prefrontal cortex (P < 0.001). A subset of these neuronal substrates was engaged in the central processing of fullness sensation. SI and SII were not activated during the fundus stimulation. In conclusion, the constellation of neuronal structures activated by fundus distension overlaps the pain matrices induced musculocutaneous pain, with the exception of the absence of SI or SII activation. This may account for the vague nature of visceral sensation/pain. Our data also confirms that the insula and amygdala may act as the central role in visceral sensation/pain, as well as in the proposed sensory-limbic model of learning and memory of pain. [source] Functional gastrointestinal disorders and visceral hypersensitivity in children and adolescents suffering from Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 11 2008Christophe Faure MD Abstract Background: Symptoms of abdominal pain are reported by children with active Crohn's disease (CD). During remissions abdominal pain improves in most children but some of them continue to experience pain. We hypothesized that these patients may suffer from protracted abdominal pain related to functional gastrointestinal disorders (FGID) and visceral hypersensitivity. The objective was to characterize the symptoms and to measure the rectal sensory threshold for pain (RSTP) by barostat in CD children and adolescents suffering from abdominal pain despite remission. Methods: Eight patients (median age 14.5 years; range 9.8,17) with quiescent CD but suffering from chronic abdominal pain were studied by rectal barostat. At the same time they completed validated questionnaires to assess FGID, anxiety, and depression. They were compared to 10 control children and 8 children with FGID also investigated in our laboratory. Results: All patients fulfilled Rome II criteria for irritable bowel syndrome (n = 5), functional abdominal pain (n = 2), and functional dyspepsia (n = 1). RSTP was significantly lower in CD patients compared to the normal controls: median (range) 25 mmHg (15,29) versus 40 mmHg (30,48) (P < 0.01). RSTP was similar in patients and children with FGID. Rectal compliance was similar in patients, children with FGID, and controls. Seven of the 8 patients had scores indicating an anxiety problem. Conclusions: Protracted abdominal pain that affects children and adolescents with quiescent CD is related to FGID associated with visceral hypersensitivity and anxiety. The incidence of FGID in children suffering from CD requires further investigation. (Inflamm Bowel Dis 2008) [source] Review article: visceral hypersensitivity in irritable bowel syndrome: molecular mechanisms and therapeutic agentsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009A. AKBAR Summary Background, Although development of visceral pain is an important defensive mechanism, hypersensitivity results in a significant clinical problem and is likely to be one of the major factors involved in the pathogenesis of abdominal and chest pain in functional bowel disorders (FBDs). Understanding of the molecular mechanisms involved in peripheral sensitization of visceral nociceptors has advanced as a result of the experimental studies, especially in animal models, which have led to knowledge and identification of key mediators and receptors. Aim, To provide a comprehensive review focused on the peripheral mechanisms believed to be responsible for sensitization and potential molecular targets for a disorder which is common, distressing and has sub-optimal treatment options. Methods, Literature review using Ovid and Pubmed from 1966. Results, There is substantial interest in the development of new drugs for treatment of FBDs in the background of advances in understanding the molecular and physiological mechanisms of visceral hypersensitivity. The potential drug targets include TPRV1, ASICs, voltage-gated sodium channels, ATP, PAR-2, cannabinoid, prostaglandin, tachykinin and 5HT3 receptors. Conclusion, It is anticipated that with advancing molecular understanding of the basis of visceral hypersensitivity, the next decade will see accelerated development of new molecules for treatment of functional bowel diseases. [source] Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndromeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009N. M. THOUA Summary Background, Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response. Aim, To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients. Methods, Nineteen patients with IBS were given amitriptyline 25,50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity). Results, Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders (P > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline ,31% vs. +2%, P < 0.03 respectively). Conclusion, In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS. [source] The view of gastroenterologists on non-cardiac chest pain in AsiaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007T. K. CHEUNG Summary Background, Non-cardiac chest pain is an important disorder in Asia. The practice and views of gastroenterologists on non-cardiac chest pain in this region are not known. Aims, To determine the current understanding, diagnostic practice and treatment strategies among gastroenterologists on the management of non-cardiac chest pain in Asia. Methods, A 24-item questionnaire was sent to gastroenterologists in Mainland China, Hong Kong, Malaysia, Indonesia, Philippines, Singapore, Taiwan and Thailand. Results, 186 gastroenterologists participated with a response rate of 74%. 98% of gastroenterologists managed patients with non-cardiac chest pain over the last 6 months. 64% felt that the number of non-cardiac chest pain patients was increasing and 85% believed that the most common cause of non-cardiac chest pain was GERD. 94% of the gastroenterologists believed that they should manage non-cardiac chest pain patients, but only 41% were comfortable in diagnosing non-cardiac chest pain. The average number of investigations performed was four in non-cardiac chest pain patients, and oesophago-gastro-duodenoscopy was the most commonly used initial test. A proton pump inhibitor was considered the first-line treatment in non-cardiac chest pain and was reported as the most effective treatment by the gastroenterologists. Conclusion, Most gastroenterologists were practicing evidence-based medicine, but frequent use of investigations and a lack of awareness of the role of visceral hypersensitivity in non-cardiac chest pain patients were noted. [source] Neurokinin-1 receptor antagonism in a human model of visceral hypersensitivityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007R. P. WILLERT Summary Background Substance P acting via the neurokinin-1 receptor is involved in the development of hyperalgesia, although studies using neurokinin-1 receptor antagonists (NK-1RA) in human somatic pain have been disappointing. Aim To evaluate whether Substance P is involved in the development of human visceral pain/hyperalgesia using a selective NK-1RA. Methods Using a validated human model of acid-induced oesophageal allodynia, pain thresholds to electrical stimulation (mA) were measured in the proximal oesophagus and the foot (somatic control), pre- and for 4 h postdistal oesophageal acid in 14 healthy subjects, using a double-blind, randomized, two-period, crossover study. Measurements were taken on the third day of dosing with either an oral NK-1RA or matching placebo, with 2 weeks washout between periods. Results Baseline pain threshold did not differ between treatments (proximal oesophagus 37 ± 7.4 mA NK-1RA vs. 38 ± 10.1 placebo P = 0.81, foot 40 ± 15 mA NK-1RA vs. 38 ± 14 placebo P = 0.68). NK-1RA did not attenuate the reduction in pain threshold in the proximal oesophagus postacid infusion (AUC,394 ± 279 NK-1RA vs. ,262 ± 397 placebo P = 0.54). Conclusions The lack of effect of NK-1RA on oesophageal pain threshold in our model does not support a role for Substance P in the development of acid-induced oesophageal allodynia. [source] Review article: uncomplicated diverticular disease of the colonALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006L. PETRUZZIELLO Summary Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect healthcare costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed. [source] Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral painNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2010H. Eutamene Abstract Background, Linaclotide is a novel, orally administered investigational drug currently in clinical development for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation. Visceral hyperalgesia is a major pathophysiological mechanism in IBS-C. Therefore, we investigated the anti-nociceptive properties of linaclotide in rodent models of inflammatory and non-inflammatory visceral pain and determined whether these pharmacological effects are linked to the activation of guanylate cyclase C (GC-C). Methods,Orally administered linaclotide was evaluated in non-inflammatory acute partial restraint stress (PRS) and acute water avoidance stress (WAS) models in Wistar rats, and in a trinitrobenzene sulfonic acid (TNBS)-induced inflammatory model in Wistar rats and GC-C null mice. Key Results,In TNBS-induced colonic allodynia, linaclotide significantly decreased the number of abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity change in response to distending pressures after TNBS. However, linaclotide had no effect on visceral sensitivity under basal conditions. In addition, linaclotide significantly decreased colonic hypersensitivity in the PRS and WAS models. In wild type (wt) and GC-C null mice, the instillation of TNBS induced similar hyperalgesia and allodynia. However, in post-inflammatory conditions linaclotide significantly reduced hypersensitivity only in wt mice, but not in GC-C null mice. Conclusions & Inferences,These findings indicate that linaclotide has potent anti-nociceptive effects in several mechanistically different rodent models of visceral hypersensitivity and that these pharmacological properties of linaclotide are exerted through the activation of the GC-C receptor. Therefore, linaclotide may be capable of decreasing abdominal pain in patients suffering from IBS-C. [source] Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptomsNEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2009J. Simpson Abstract:, Some patients with colonic diverticula suffer recurrent abdominal pain and exhibit visceral hypersensitivity, though the mechanism is unclear. Prior diverticulitis increases the risk of being symptomatic while experimental colitis in animals increases expression of neuropeptides within the enteric nervous system (ENS) which may mediate visceral hypersensitivity. Our aim was to determine the expression of neuropeptides within the ENS in diverticulitis (study 1) and in patients with symptomatic disease (study 2). Study 1 , Nerves in colonic resection specimens with either acute diverticulitis (AD, n = 16) or chronic diverticulitis (CD, n = 16) were assessed for neuropeptide expression recording % area staining with protein gene product (PGP9.5), substance P (SP), neuropeptide K (NPK), pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP) and galanin. Study 2 , Seventeen symptomatic and 15 asymptomatic patients with colonic diverticula underwent flexible sigmoidoscopy and multiple peridiverticular mucosal biopsies. Study 1, Neural tissue, as assessed by PGP staining was increased to a similar degree in circular muscle in both AD and CD. The CD specimens showed significant increases in the immunoreactivity of SP, NPK and galanin in both mucosal and circular muscle layer compared with controls. Study 2 , Mucosal histology was normal and PGP9.5 staining was similar between groups however patients with symptomatic diverticular disease demonstrated significantly higher levels of SP, NPK, VIP, PACAP and galanin within the mucosal plexus. Patients with symptomatic diverticular disease exhibit increased neuropeptides in mucosal biopsies which may reflect resolved prior inflammation, as it parallels the changes seen in acute and chronic diverticulitis. [source] Corticotropin-releasing hormone receptor 1 antagonist blocks colonic hypersensitivity induced by a combination of inflammation and repetitive colorectal distensionNEUROGASTROENTEROLOGY & MOTILITY, Issue 10 2008K. Saito-nakaya Abstract, Gastroenteritis is one of the risk factors for developing irritable bowel syndrome (IBS). However, the precise mechanism of postinfectious IBS is still unknown. We tested the hypothesis that a combination of previous inflammation and repetitive colorectal distention (CRD) makes the colon hypersensitive and that treatment with a corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist blocks this colonic hypersensitivity. Rats were pretreated with vehicle or 2,4,6-trinitrobenzene sulphonic acid (TNBS) 6 weeks before CRD. For the CRD experiment, the colorectum was distended once a day for six consecutive days. The CRH-R1 antagonist (CP-154,526, 20 mg kg,1) or vehicle was injected subcutaneously 30 min before CRD. Visceral perception was quantified as visceromotor response (VMR) using an electromyograph. For histological examination, the rats were killed on the last day of CRD experiment, and haematoxylin and eosin-staining of colon segments was performed. Although from the first to the third day of CRD, VMRs increased in both the vehicle-treated rats and TNBS-treated rats, they were significantly higher in TNBS-treated rats than those in vehicle-treated controls. On the fifth day of CRD, however, VMRs in the vehicle-treated rats were significantly greater than those in TNBS-treated rats. Pretreatment of rats with CP-154,526 significantly attenuated the increase in VMR induced by repetitive CRD with previous inflammation. Finally, we found that repetitive CRD and repetitive CRD after colitis induced visceral inflammation. These results indicate that a combination of previous inflammation and repetitive CRD induces visceral hypersensitivity and that a CRH-R1 antagonist attenuates this response in rats. [source] Differential changes in brain-derived neurotrophic factor and extracellular signal-regulated kinase in rat primary afferent pathways with colitisNEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2008L.-y. Qiao Abstract, Brain-derived neurotrophic factor (BDNF) has been postulated to participate in inflammation-induced visceral hypersensitivity by modulating the sensitivity of visceral afferents through the activation of intracellular signalling pathways such as the extracellular signal-regulated kinase (ERK) pathway. In the current study, we assessed the expression levels of BDNF and phospho-ERK in lumbosacral dorsal root ganglia (DRG) and spinal cord before and during tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in rats with real-time PCR, ELISA, western blot and immunohistochemical techniques. BDNF mRNA and protein levels were increased in L1 and S1 but not L6 DRG when compared with control (L1: two- to five-fold increases, P < 0.05; S1: two- to three-fold increases, P < 0.05); however, BDNF protein but not mRNA level was increased in L1 and S1 spinal cord when compared with control. In parallel, TNBS colitis significantly induced phospho-ERK1/2 expression in L1 (four- to five-fold, P < 0.05) and S1 (two- to three-fold, P < 0.05) but not in L6 spinal cord levels. Immunohistochemistry results showed that the increase in phospho-ERK1/2 expression occurred at the region of the superficial dorsal horn and grey commisure of the spinal cord. In contrast, there was no change in phospho-ERK5 in any level of the spinal cord examined during colitis. The regional and time-specific changes in the levels of BDNF mRNA, protein and phospho-ERK with colitis may be a result of increased transcription of BDNF in DRG and anterograde transport of BDNF from DRG to spinal cord where it activates intracellular signalling molecules such as ERK1/2. [source] 5-HT receptors and visceral hypersensitivity , 2B or not 2B, that is the question?NEUROGASTROENTEROLOGY & MOTILITY, Issue 5 2006D. Grundy First page of article [source] Visceral sensation and colitis: inflammation and hypersensitivity do not always go hand in handNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2006K. A. Sharkey Abstract, Visceral sensitivity and inflammation are discussed in relation to novel observations in the current issue of the Journal by Larsson and her colleagues. This paper shows that neither acute nor chronic intestinal inflammation initiated by dextran sodium sulfate is associated with an increase in visceral sensitivity to balloon distension in mice. These findings are discussed in the context of recent work highlighting the role of mast cells, the induction of endogenous antinociceptive pathways and the role of altered bacterial flora in visceral hypersensitivity. [source] Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunctionNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2005J. Wheatcroft Abstract, Patients with postinfective irritable bowel syndrome and Trichinella spiralis -infected mice share many features including visceral hypersensitivity and disordered motility. We assessed enterochromaffin (EC) numbers and serotonin transporter (SERT) using National Institute of Health (NIH) female mice studied for up to 56 days post- T. spiralis infection. The effects of steroid treatment and the T-cell dependence of the observed responses were assessed by infection of hydrocortisone-treated or T-cell receptor knock out [TCR (,×,) KO] animals. Enterochromaffin cell density in uninfected animals increased from duodenum 10.0 cells mm,2 (5.9,41.0) to colon 61.8. (46.3,162) cells mm,2P < 0.0001. Infection increased duodenal and jejunal counts which rose to 37.3 (22,57.7) cells mm,2 and 50.6 (7,110.8) cells mm,2, respectively, at day 14. Infection significantly reduced jejunal SERT expression, with luminance values falling from 61.0 (45.1,98.3) to a nadir of 11.6 (0,36.0) units at day 9, P < 0.001. Specific deficiencies in all T cells reduced EC hyperplasia and abrogated infection-induced mastocytosis. Thus infection induced inflammation increases EC numbers, as has been reported in PI-IBS, and reduces SERT. This may increase mucosal 5HT availability and contribute to the clinical presentation of PI-IBS. [source] Evoked Human Oesophageal Hyperalgesia: A Potential Tool for Analgesic Evaluation?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Anne Estrup Olesen Therefore, in the development and testing of analgesics for the treatment of visceral pain, it is important to establish an experimental pain model of visceral hypersensitivity. Such a model will mimic the clinical situation to a higher degree than pain models where the receptors and peripheral afferents are briefly activated as with, for example, electrical, thermal, and mechanical stimulations. In this study, a model to evoke experimental hyperalgesia of the oesophagus with a combination of acid and capsaicin was introduced. The study was a randomised, double-blind, cross-over study. Fifteen healthy volunteers were included. Sensory assessments to mechanical, heat, and electrical stimulations were done in the distal oesophagus, before and after perfusion with a 200 ml solution of acid+capsaicin (180 ml HCL 0.1 M and 2 mg capsaicin in 20 ml solvent) or saline. Oesophageal pain assessment and referred pain areas were evaluated. There were reproducible pain assessments between repetitions within the same day and between days (all P > 0.05). Acid+capsaicin perfusion induced 56% reduction of the pain threshold to heat (P = 0.04), 19% reduction of the pain threshold to electrical stimuli (P < 0.001), 78% increase of the referred pain areas to mechanical stimulation (P < 0.001) and 52% increase of the referred pain areas to electrical stimulus (P = 0.045). All volunteers were sensitised to one or more modalities by acid+capsaicin. The model was able to evoke consistent hyperalgesia and may be useful in future pharmacological studies. [source] | ||||||||||