Home About us Contact
|
Home About us Contact | ||
|
|
||
Visceral Sensitivity (visceral + sensitivity)
Selected AbstractsVisceral 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] Rectal sensorimotor characteristics in female patients with idiopathic constipation with or without paradoxical sphincter contractionNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2003C. E. J. Sloots Abstract, Patients with chronic constipation fulfilling the Thompson criteria can show paradoxical sphincter contraction. Aim of this study was to evaluate rectal sensorimotor characteristics in patients with constipation with or without paradoxical sphincter contraction. Thirty female patients with chronic constipation and 22 female controls were investigated with anal manometry and rectal barostat. Paradoxical sphincter contraction was shown with manometry as a paradoxical increase of anal pressure during straining. Visceral sensitivity and compliance were tested by intermittent and continuous pressure-controlled distension. Patients were classified according to their sensations and compliance into normal, hypersensitive, reduced compliant, insensitive or excessive compliant rectum. Postprandial rectal response (PRR) and phasic volume events (PVEs) were registered for 1 h after a 600-kCal meal. Paradoxical sphincter contraction was found in 13 (43%) patients. In these patients, rectal sensitivity scores were higher (P = 0.045) than in patients without paradoxical contractions, but rectal compliance was not different. In 90% of patients an abnormal rectal sensitivity or compliance was found: excessively compliant in 35%, reduced compliant in 10%, hypersensitive in 27% and hyposensitive in 17%. Both patients with constipation (11%; P = 0.042) and controls (25%; P = 0.002) exhibited the presence of a postprandial rectal response. This response was not significantly different between idiopathic constipation, paradoxical sphincter contraction and controls. Patients with rectal hypersensitivity had lower response than other patients (P = 0.04). Patients with constipation had fewer basal PVEs compared controls (P = 0.03). Postprandial PVEs increased in both patients (P = 0.014) and controls (P < 0.001). Postprandial rectal response and PVE were not different in patients with or without paradoxical sphincter contraction. A total of 90% of female patients with idiopathic constipation show an abnormality in rectal sensation or compliance. The postprandial rectal response was comparable between patients with constipation and controls, however, PVEs were diminished. Patients with paradoxical sphincter contraction had higher rectal sensitivity but an unaltered compliance and postprandial rectal response. Future trials should investigate whether the classification of rectal abnormalities in patients with constipation has clinical importance. [source] Changes in intestinal motility, visceral sensitivity and minor mucosal inflammation after fasting therapy in a patient with irritable bowel syndromeJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2006Michiko Kano [source] Nerve Growth Factor Secretion in Cultured Enteric Glia Cells is Modulated by Proinflammatory CytokinesJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2006G. B. T. Von Boyen The enteric nervous system is composed of neurones and glial cells. These enteric glia cells (EGC) appear to be essential for the maintenance of gut homeostasis and mucosal integrity. Neurotrophin nerve growth factor (NGF) also plays an important role for the gut integrity by regulating sensory and inflammatory processes in the intestines. Here, we demonstrate EGCs as one source of NGF and show increased levels of NGF mRNA/protein and tropomyosin receptor kinase A (TrkA) mRNA in cultured EGCs upon stimulation with proinflammatory cytokines and lipopolysaccharides. NGF is continuously secreted from cultured EGCs and proinflammatory cytokines and lipopolysaccharides stimulate the secretion of this neurotrophin in a time- and dose- dependent manner, whereas interleukin-4 had no effect on NGF expression. Furthermore, NGF secretion was sustained for more than 12 h after withdrawal of the proinflammatory cytokines, suggesting the involvement of transcriptional and/or translational processes. Thus, the release of proinflammatory cytokines can increase NGF secretion by EGCs and leads to a higher expression of TrkA in EGCs. NGF, in turn, can increase visceral sensitivity and, on the other hand, appears to improve gut inflammation. Therefore, NGF secreting EGCs may play a key role in modulating visceral sensitivity and might be involved in inflammatory processes of the gut. [source] Lactose intolerance in patients with chronic functional diarrhoea: the role of small intestinal bacterial overgrowthALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010J. ZHAO Aliment Pharmacol Ther,31, 892,900 Summary Background, Many studies report a high prevalence of lactose intolerance in patients with functional, gastrointestinal disease. Aim, To evaluate the role of small intestinal bacterial overgrowth (SIBO) in condition of lactose intolerance and the mechanism by which SIBO may impact lactose tolerance in affected patients. Methods, Consecutive out-patients with chronic functional diarrhoea (CFD) and healthy controls underwent a validated 20 g lactose hydrogen breath test (HBT). Patients completed also a 10 g lactulose HBT with concurrent assessment of small bowel transit by scintigraphy. Results, Lactose malabsorption was present in 27/31 (87%) patients with CFD and 29/32 (91%) healthy controls (P = 0.708). From the patient group 14/27 (52%) had lactose intolerance and 13/27 (48%) experienced no symptoms (lactose malabsorption controls). Only 5 (17%) healthy controls reported symptoms (P < 0.01). The oro-caecal transit time was similar between patient groups with or without symptoms (P = 0.969). SIBO was present in 11 (41%) subjects and was more prevalent in lactose intolerance than in lactose malabsorption [9/14 (64%) vs. 2/13 (15%), P = 0.018]. Symptom severity was similar in lactose intolerance patients with and without SIBO (P = 0.344). Conclusions, Small intestinal bacterial overgrowth increases the likelihood of lactose intolerance in patients with CFD as a direct result of lactose fermentation in the small intestine, independent of oro-caecal transit time and visceral sensitivity. [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] Effect of long-term treatment with octreotide on rectal sensitivity in patients with non-constipated irritable bowel syndromeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007T. K. KLOOKER Summary Background, Acute administration of octreotide reduces visceral perception and therefore has been suggested as potential treatment for irritable bowel syndrome. Whether prolonged treatment with octreotide also reduces visceral sensitivity and improves gastrointestinal symptoms remains, however, unknown. Aim, To investigate the effect of a slow release preparation of octreotide on rectal sensitivity and symptoms in irritable bowel syndrome patients. Methods, Forty-six non-constipated irritable bowel syndrome patients (52% female, 19,63 years) participated. Before and after 8 weeks of treatment with octreotide (Sandostatin LAR 20 mg i.m.) or placebo, patients underwent a barostat study to assess the rectal sensitivity. During a 2-week run-in period and treatment, abdominal pain, defecation frequency, consistency and symptom relief were scored weekly. Results, Octreotide, but not placebo, significantly increased the threshold for first sensation. Thresholds for urge to defecate and discomfort/pain and rectal compliance were not altered by either treatment. Octreotide improved stool consistency compared with placebo (loose stools after eight weeks: octreotide: 52%, placebo: 81%, P < 0.05). In contrast, abdominal pain and defecation frequency were not affected. Conclusions, Although the threshold of first rectal sensation increased and stool consistency improved, long-term treatment with octreotide, at least at the current dose used, has no visceral analgesic effect and fails to improve irritable bowel syndrome symptoms. [source] Prucalopride, a systemic enterokinetic, for the treatment of constipationALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2002A. V. Emmanuel Summary Background : Laxatives are frequently ineffective in treating constipation. An alternative therapeutic approach is to target serotonin-4 receptors, which are involved in initiating peristalsis. Aim : In a double-blind, placebo-controlled trial, to assess the efficacy and safety of a systemically active serotonin-4 agonist, prucalopride. Methods : Seventy-four women with constipation were stratified into slow or normal transit groups, and each group was randomized to receive either placebo or 1 mg prucalopride daily for 4 weeks. A bowel function diary was maintained. Whole-gut and orocaecal transit, visceral sensitivity, quality of life and psychological state were assessed before and after treatment. Results : Prucalopride, not placebo, increased spontaneous stool frequency (P=0.008) and reduced time to first stool (P < 0.001). Prucalopride reduced the number of retained markers in all patients compared to placebo (P=0.004). Prucalopride reduced the mean number of retained markers in slow transit (P=0.069), but did not alter the marker count in normal transit (P=0.86). Orocaecal transit was accelerated by prucalopride, not placebo (P=0.004). Prucalopride, notplacebo, increased rectal sensitivity to distension (urge volume, P=0.01) and electrical stimulation (P=0.001). Prucalopride significantly improved several domains of the Short Form Health Status Survey and the disease-specific quality of life. Adverse effects were similar for prucalopride and placebo. Conclusions : Prucalopride improves symptoms, upper gut transit and gut sensitivity in constipated patients with both slow and normal transit. It improves transit in patients with slow transit. These changes are associated with improved well-being. [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] Chemosensitivity of the human gastrointestinal tract in health and in diseaseNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2007J. Tack Abstract, Although visceral sensitivity in man comprises chemosensitivity, thermosensitivity and mechanosensitivity, only the latter has been intensively studied. Studies in health have aimed at characterising the type of mechanoreceptors involved in visceral mechanosensitivity,. Several authors have studied the prevalence and relevance to the symptom pattern of hypersensitivity to visceral balloon distention in patients with functional gastrointestinal disorders. Chemosensitivity of the gastrointestinal tract in man has received much less attention. In this issue of Neurogastroenterology and Motility, intraluminal application of capsaicin is described as a tool to study chemosensitivity of the proximal gastrointestinal tract. The authors report how activation of chemosensitive pathways induces symptoms that differ from those induced by activation of mechanosensitive pathways, and propose to use capsaicin as a tool to study the prevalence and role of hypersensitivity to visceral chemosensitivity in patients with functional gastrointestinal disorders. Our current knowledge of visceral chemosensitivity of the human gastrointestinal tract in health and in disease is reviewed, with a specific focus on the interaction between mechano- and chemosensitive pathways. [source] Long-lasting changes in small intestinal transport following the recovery from Trichinella spiralis infectionNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2006K. Venkova Abstract, Changes in intestinal motility and visceral sensitivity are found after resolution of acute enteric inflammation. The study investigates whether a transient nematode-induced intestinal inflammation may result in long-lasting remodelling of epithelial transport. Ferrets infected with Trichinella spiralis or sham-infected animals were euthanized on day 10, 30 or 60 postinfection (PI) and the jejunum was isolated. The net transport of electrolytes was measured electrophysiologically as transmucosal short-circuit current (Isc) and responses to electrical field stimulation (EFS: 1,32 Hz) or secretagogues were investigated. Myeloperoxidase (MPO) activity, a marker of mucosal inflammation, was maximal during the enteric stage of T. spiralis infection (day 10 PI) and returned to normal on days 30 and 60 PI. Mucosal inflammation caused a reduction in basal Isc, increased electrical conductance (G) and decreased the maximal responses to EFS, carbachol or histamine. On days 30 and 60 PI the inflammation resolved and basal electrogenic transport appeared normal; however, the secretion induced by EFS, carbachol or histamine remained suppressed. Moreover, EFS-induced responses were shifted from predominantly cholinergic in controls to non-cholinergic in the infected animals. The results suggest that a transient small intestinal inflammation causes a long-term remodelling of epithelial function. [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] Oxytocin stimulates colonic motor activity in healthy womenNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2004B. Ohlsson Abstract, The effects of oxytocin in the gastrointestinal tract are unclear. The aim of this study was to examine the effect of infusion of oxytocin on colonic motility and sensitivity in healthy women. Fourteen healthy women were investigated twice. A 6-channel perfusion catheter, with three recording points (2 cm apart) proximally and three recording points distally to a barostat balloon, was inserted to the splenic flexure. An intestinal feeding tube was placed in the mid-duodenum. A 90-min duodenal lipid infusion of 3 kcal min,1 was administered. Thirty minutes after the start of the lipid infusion, the subject randomly received either 20 or 40 mU min,1 of oxytocin, or isotonic saline as intravenous infusions for 90 min. Meanwhile, the colonic motility was recorded. During the last 30 min of oxytocin and saline infusion, the visceral sensitivity to balloon distensions was examined. During lipid infusion the number of antegrade contractions per hour was 0.7 ± 0.3 after saline and 3.9 ± 1.4 after oxytocin (P = 0.03), indicating more pronounced lumen-occlusive contractile activity after oxytocin administration. Some of these consisted of high-amplitude (> 103 mmHg in amplitude) antegrade contractions. Lipid infusion evoked a decrease of the balloon volume, reflecting increased colonic tone, but there was no difference between saline and oxytocin. Sensory thresholds did not differ significantly between saline and oxytocin. Infusion of oxytocin stimulates antegrade peristaltic contractions in stimulated colon in healthy women. The effects of oxytocin on colonic motor activity deserve to be further explored, especially in patients with colonic peristaltic dysfunction. [source] Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammationBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008K L Wright The emerging potential for the cannabinoid (CB) system in modulating gastrointestinal inflammation has gained momentum over the last few years. Traditional and anecdotal use of marijuana for gastrointestinal disorders, such as diarrhoea and abdominal cramps is recognized, but the therapeutic benefit of cannabinoids in the 21st century is overshadowed by the psychoactive problems associated with CB1 receptor activation. However, the presence and function of the CB2 receptor in the GI tract, whilst not yet well characterized, holds great promise due to its immunomodulatory roles in inflammatory systems and its lack of psychotropic effects. This review of our current knowledge of CB2 receptors in the gastrointestinal tract highlights its role in regulating abnormal motility, modulating intestinal inflammation and limiting visceral sensitivity and pain. CB2 receptors represent a braking system and a pathophysiological mechanism for the resolution of inflammation and many of its symptoms. CB2 receptor activation therefore represents a very promising therapeutic target in gastrointestinal inflammatory states where there is immune activation and motility dysfunction. British Journal of Pharmacology (2008) 153, 263,270; doi:10.1038/sj.bjp.0707486; published online 1 October 2007 [source] | ||||||||||