Best Pract Res Clin Gastroenterol. 2004 Aug;18(4):747-71. Related Articles, Links Alterations of sensori-motor functions of the digestive tract in the pathophysiology of irritable bowel syndrome.Delvaux M.Department of Internal Medicine and Digestive Pathology, CHU de Brabois, F-54511 Vandoeuvre-les-Nancy, France.Pathophysiology of irritable bowel syndrome (IBS) is based upon multiple factors that have been organised in a comprehensive model centred around the brain-gut axis. The brain-gut axis encompasses nerve pathways linking the enteric and the central nervous systems and contains a large proportion of afferent fibres. Functionally and anatomically, visceral nerves are divided in to two categories: the parasympathetic pathways distributing to the upper gut through the vagi and to the hindgut, through the pelvic and pudendal nerves, and the sympathetic pathways, arising form the spinal cord and distributing to the midgut via the paravertebral ganglia. Several abnormalities of gut sensori-motor function have been described in patients with IBS. Abnormal motility patterns have been described at the intestinal and colonic levels. Changes in colonic motility are mainly related to bowel disturbances linked to IBS but do not correlate with pain. More recently, visceral hypersensitivity has been recognised as a main characteristic of patients with IBS. It is defined by an exaggerated perception of luminal distension of various segments of the gut and related to peripheral changes in the processing of visceral sensations as well as modulation of perception by centrally acting factors including mood and stress. Viscero-visceral reflexes link the two edges of the brain-gut axis and may account for the origin of symptoms in some pathological conditions. Recent advances in the understanding of the role of myenteric plexus allowed recognition of several neurotransmitters involved at the level of both the afferent and efferent pathways. Targeting the receptors of these neurotransmitters is a promising way for development of new treatments for IBS.PMID: 15324712 Eur J Pain. 2004 Oct;8(5):451-463. Related Articles, Links Sex-based differences in gastrointestinal pain.Mayer EA, Berman S, Chang L, Naliboff BD.Departments of Medicine, Psychiatry and Biobehavioral Sciences, CNS: Center for Neurovisceral Sciences and Women's Health, UCLA Division of Digestive Diseases, UCLA and VA GLAHS, Bldg. 115/CURE, WLA VA Medical Center, 11301 Wilshire Blvd., Room 213, Los Angeles, CA 90073, USA.Recent interest has focused on sex-related differences in irritable bowel syndrome (IBS) physiology and treatment responsiveness to novel pharmacologic therapies. Similar to a variety of other chronic pain conditions and certain affective disorders, IBS is more prevalent amongst women, both in population-based studies as well as in clinic-based surveys. Non-painful gastrointestinal symptoms, constipation and somatic discomfort are more commonly reported by female IBS patients. While perceptual differences to rectosigmoid stimulation are only observed following repeated noxious stimulation of the gut, sex-related differences in certain sympathetic nervous system (SNS) responses to rectosigmoid stimulation are consistently seen. Consistent with experimental findings in animals, current evidence is consistent with a pathophysiological model which emphasizes sex-related differences in autonomic and antinociceptive responses to certain visceral stimuli. PMID: 15324776 This was the VSL# study"But Dr. Fedorak cautioned that "we don't know how they work. They appear to strengthen the mucosal barrier of the bowel and improve immune function. And we don't know which probiotics to use or in what combination.""also this was a newer VSL 3 study" Aliment Pharmacol Ther. 2003 Apr 1;17(7):895-904. Related Articles, Links A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome.Kim HJ, Camilleri M, McKinzie S, Lempke MB, Burton DD, Thomforde GM, Zinsmeister AR.Clinical Enteric Neuroscience Translational & Epidemiological Research Program, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.AIM: To investigate the effects of a probiotic formulation, VSL#3, on gastrointestinal transit and symptoms of patients with Rome II irritable bowel syndrome with predominant diarrhoea. METHODS: Twenty-five patients with diarrhoea-predominant irritable bowel syndrome were randomly assigned to receive VSL#3 powder (450 billion lyophilized bacteria/day) or matching placebo twice daily for 8 weeks after a 2-week run-in period. Pre- and post-treatment gastrointestinal transit measurements were performed in all patients. Patients recorded their bowel function and symptoms daily in a diary during the 10-week study, which was powered to detect a 50% change in the primary colonic transit end-point. RESULTS: There were no significant differences in mean gastrointestinal transit measurements, bowel function scores or satisfactory global symptom relief between the two treatment groups, pre- or post-therapy. Differences in abdominal bloating scores between treatments were borderline significant (P = 0.09, analysis of covariance). Further analysis revealed that abdominal bloating was reduced (P = 0.046) with VSL#3 mean post- minus pre-treatment score, - 13.7; 95% confidence interval (CI), - 2.5 to - 24.9, but not with placebo (P = 0.54) (mean post- minus pre-treatment score, - 1.7; 95% CI, 7.1 to - 10.4). With the exception of changes in abdominal bloating, VSL#3 had no effect on other individual symptoms: abdominal pain, gas and urgency. All patients tolerated VSL#3 well. CONCLUSION: VSL#3 appears to be promising in the relief of abdominal bloating in patients with diarrhoea-predominant irritable bowel syndrome. This is unrelated to an alteration in gastrointestinal or colonic transit.Publication Types: Clinical Trial Randomized Controlled Trial PMID: 12656692Med Sci Monit. 2004 Jun;10(6):RA125-31. Epub 2004 Jun 01. Related Articles, Links The brain-gut axis in irritable bowel syndrome--clinical aspects.Mach T.Department of Infectious Diseases and Hepatology, Jagiellonian University School of Medicine, ul. Sniadeckich 10, 31-153 Krakow, Poland. mstmach###cyf-kr.edu.plIrritable bowel syndrome (IBS) is the most common chronic gastrointestinal (GI) disorder, affecting about 20% of the world's population. Chronic abdominal pain or discomfort relieved by defecation and associated with altered bowel habits are the mainstay in diagnosis. The pathophysiology of IBS remains unknown. This biopsychosocial disorder involves dysregulation of the nervous system, altered intestinal motility, and increased visceral sensitivity. All of these result from dysregulation of the bidirectional communication between the gut with its enteric nervous system and the brain (the brain-gut axis), modulated by various psychosocial and environmental factors (e.g. infection, inflammation). Numerous neurotransmitters are found in the brain and gut that regulate GI activities, including 5-hydroxytryptamine (5-HT, serotonin) and its 5-HT3 and 5-HT4 receptors. The current approach to IBS patients is based on a positive diagnosis of the symptom complex, exclusion of underlying organic disease, and institution of a therapeutic trial. Traditional symptomatic treatment has included antidiarrheals, laxatives and bulking agents/fiber, low-dose tricyclic antidepressants, antispasmodics for pain, and "alternative" therapies (e.g. psychotherapy, hypnotherapy). The scientific evidence supporting this therapy is limited. Novel approaches include visceral analgesics and serotonin agonists and antagonists. In patients with severe diarrhea, 5-HT3 receptor antagonists (e.g. alosetron) and selective M3-type anticholinergics are indicated, in constipation 5-HT4 agonists (e.g. tegaserod), and in pain alfa2-adrenergics (e.g. clonidine), cholecystokinin antagonists, kappa-opioid agonists (e.g. fedotozine), and neurokinin antagonists; some of these agents are still being investigated. Understanding the brain-gut axis is crucial in the development of effective therapies for IBS.Publication Types: Review Review, Tutorial PMID: 15173682Irritable Bowel Syndrome (IBS), which is classified as a functional gastrointestinal disorder, is a chronic condition of the lower gastrointestinal tract (Figure 1) that affects as many as 15% of adults in the United States. Not easily characterized by structural abnormalities, infection, or metabolic disturbances, the underlying mechanisms of IBS have for many years remained unclear. Recent research, however, has lead to an increased understanding of IBS. As a result, IBS is now considered an organic and, most likely, neurologic bowel disorder. IBS is often referred to as spastic, nervous or irritable colon. Its hallmark is abdominal pain or discomfort associated with a change in the consistency and/or frequency of bowel movements. Although the causes of IBS have not to date been fully elucidated, it is believed that symptoms can occur as a result of a combination of factors, including visceral hypersensitivity, altered bowel motility, neurotransmitters imbalance, infection and psychosocial factors (Figure 2). "
http://hopkins-gi.nts.jhu.edu/pages/latin/...se=43&lang_id=1 Rome"Irritable Bowel Syndrome: How far do you go in the Workup?Douglas A. Drossman, M.D.Professor of Medicine and PsychiatryCo-Director, UNC Center for Functional GI and Motility DisordersDivision of Digestive DiseasesUniversity of North Carolina at Chapel Hill"For example, there is a subgroup of patients, called "post-infectious IBS" who appear to respond to an enteric infection such as campylobactor jejuni with an increased inflammatory cell response (22). This is associated with activating enterochromaffin cells to produce 5HT, and CD3 cells to produce cytokines, which in turn leads to enhanced motility and lowered visceral sensation thresholds (22;23). But microscopic inflammation cannot be a diagnostic marker for IBS because it does not typically produce pain in those who have it. All patients with active celiac disease have microscopic inflammation, but a large proportion do not have abdominal pain, and patients with ulcerative colitis who also have microscopic inflammation when compared to patients with IBS appear to have higher pain thresholds (24) . In individuals with these disorders, there may be central nervous system counter-regulatory measures responding to the peripheral pain/inflammatory processes that increase pain thresholds. With regard to IBS, the gut-related effects of microscopic inflammation may be only one component of a dysfunctional brain-gut system. In addition, and often in response to stress, there may be a failure to activate descending pain inhibitory systems that enable the clinical experience of pain and other symptoms that typify this disorder (25). In one prospective study of post-infectious IBS, it was found that those who retained their symptoms 3-months after an enteric infection had not only increased mucosal cellularity, but also had increased psychosocial distress at the time of the infection. Furthermore, lowered visceral sensation thresholds and increased motility were present after the infection regardless of whether or not the patients retained their symptoms (26). Therefore, the microscopic inflammation and its physiological effects on motility and sensation contribute to, but are not always sufficient for the clinical expression of IBS pain. At least for post-infectious IBS this provides some evidence that psychological distress alters brain pain regulatory pathways to amplify incoming visceral signals leading to the full clinical expression of this syndrome "
http://www.romecriteria.org/reading1.html So it does not seem to be caused ONLY by inflammation and infection and the inflammation seen are specific cells called mast cells and they are very connected to stress and fighting infection. Hence why there is a big already known correlation between gut infection and being stressed at the time of infection leading to IBS in PI IBS after the RESOLUTION of the Initial INFECTION. Probiotics have shown to reduce gas pain and bloating in some studies, but this is at the level of the gut and for some reasons they are alreay aware of, because the colon has pressure senisive cells, thats how the colon works and I don't think you have study the basics of this fact at all. What probiotics and I am not agasint them in the slightest haven't shown is any effect on the impairments and resolution of those impairments of pain in the brain of IBS patients yet. They have shown they help at the gut level somewhat, but only on bloating and pain, probably through gas reduction and possibly on some immune function which in turn would help pain at the gut level, so as not to signal pain to the brain.But there is still impairment of certain brain centers they have found in IBS and not control subjects which they have a ton of information on to implicate in IBS symptoms. Even that chrnoic stressors are contributing to if not causing the inflammation of those mast cells without a pathogen.and Robin Spiller is a leading expert on Inflammtion and IBS and on PI IBS."Best Pract Res Clin Gastroenterol. 2004 Aug;18(4):641-61. Related Articles, Links Inflammation as a basis for functional GI disorders.Spiller RC.Division of Gastroenterology, The Wolfson Digestive Disease Centre, University Hospital, Nottingham NG7 2UH, UK.The term 'Functional diseases' implies symptoms arising from an organ without overt pathology. However this is more apparent than real since inflammation often leaves changes in nerves and mucosal function only apparent with specialised techniques. Acute onset functional dyspepsia accounts for around 1/5 of functional dyspepsia and is characterised by early satiety, nausea, vomiting and weight loss. Impaired postcibal fundal accommodation may underlie some of these symptoms. Post infectious gastroparesis is much rarer and is associated with markedly delayed gastric emptying and antral hypomotility. Approximately 1/10 of IBS cases describe a post infectious onset. Post infectious IBS is typically of the diarrhoea-predominant type. Post inflammatory functional diseases tend to be associated with less psychological abnormalities and have a better prognosis than other functional diseases. There are isolated anecdotal reports of symptom response to anti-inflammatory treatments but larger controlled trials are needed.PMID: 15324705 "Gastroenterology. 2003 Dec;125(6):1651-9. Related Articles, Links Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS.Dunlop SP, Jenkins D, Neal KR, Spiller RC.Wolfson Digestive Diseases Centre, University Hospital, Nottingham, England.BACKGROUND & AIMS: Both psychological and mucosal changes (increased enterochromaffin EC cells and T lymphocytes) have been associated with postinfectious irritable bowel syndrome (PI-IBS). However, previous studies have been underpowered to determine the relative importance of these changes in predicting the development of PI-IBS. Our aim was to prospectively determine the relative importance of both psychological and histologic factors in the development of PI-IBS after Campylobacter infection. METHODS: Questionnaires detailing psychological and bowel symptoms were sent to 1977 patients 3 months after infection. Twenty-eight patients with new-onset PI-IBS, 28 age- and sex-matched patient controls who were asymptomatic after infection, and 34 healthy volunteers underwent rectal biopsy, which was assessed for serotonin-containing EC cells, mast cells, and lamina propria T lymphocytes. RESULTS: PI-IBS, predominantly of the diarrhea-predominant subtype, occurred in 103 of 747 (13.8%) of those infected. EC cell counts per high-power field (hpf) were higher in patients with PI-IBS (35.8 +/- 1.2) compared with patient controls (30.6 +/- 1.9; P = 0.022) and volunteers (29.1 +/- 1.8; P = 0.006). Lamina propria T lymphocytes per hpf were higher in patients with PI-IBS (127.1 +/- 8.7) and patient controls (113.4 +/- 6.2) in contrast to healthy volunteers (97.1 +/- 5.7) (P = 0.006 and P = 0.058, respectively). Anxiety, depression, and fatigue were significantly increased in patients with PI-IBS compared with patient controls. Multivariate analysis indicated that increased EC cell counts and depression were equally important predictors of developing PI-IBS (relative risk, 3.8 and 3.2 for each standard deviation increase in respective values). CONCLUSIONS: Both increased EC cells and depression are important independent predictors of developing PI-IBS. PMID: 14724817EC cells store the majority of serotonin in the gut. Serotonin is majorally implicated in IBS!!!!"Am J Gastroenterol. 2003 Jul;98(7):1578-83. Related Articles, Links Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome.Dunlop SP, Jenkins D, Spiller RC.Division of Divisions of Gastroenterology, University Hospital, Nottingham, United Kingdom.OBJECTIVE: Irritable bowel syndrome after gastroenteritis is well recognized. Our aim was to determine whether postinfective IBS (PI-IBS) has histological or clinical features that are distinct from those of IBS patients with no history of preceding infection. METHODS: A total of 75 consecutive IBS outpatients and 36 healthy control subjects completed a questionnaire detailing symptoms, mode of onset, and previous psychiatric history. All underwent a full diagnostic workup including rectal biopsy, which included immunostaining and quantification for lamina propria or intraepithelial T lymphocytes, serotonin-containing enterochromaffin (EC), and mast cells. Patients were divided according to onset of symptoms into PI-IBS (n = 23) or non-PI-IBS (n = 52) patients. RESULTS: Diarrhea predominance occurred more frequently in PI-IBS (70%) than in non-PI-IBS (42%) patients (p = 0.03). A history of previous treatment for anxiety or depression was present in 26% of PI-IBS patients compared to 54% of non-PI-IBS (p = 0.02). Biopsy results for all patients were normal using conventional criteria; however, quantification revealed that PI-IBS showed increased EC cells compared to those of non-PI-IBS patients (p = 0.017) and controls (p = 0.02). Lamina propria T lymphocytes were increased in PI-IBS (p = 0.026) and non-PI-IBS (p = 0.011) patients compared to controls. Mast cells were increased in non-PI-IBS patients (p = 0.054) compared to controls. CONCLUSIONS: Individuals with PI-IBS are a clinically distinct subgroup characterized by diarrheal symptoms, less psychiatric illness, and increased serotonin-containing EC cells compared to those with non-PI-IBS.PMID: 12873581 ""Curr Treat Options Gastroenterol. 2003 Aug;6(4):329-337. Related Articles, Links Treatment of Irritable Bowel Syndrome.Spiller RC.Department of Gastroenterology, University Hospital, Derby Road, Nottingham NG7 2UH, UK. robin.spiller###nottingham.ac.ukIrritable bowel syndrome (IBS) is an extremely common cause of consultation, and at present is diagnosed on the basis of symptoms and a few simple exclusion tests. Exclusion diets can be successful, but many patients have already attempted and failed such treatments before consulting. Anxiety and somatization may be an important driver of consultation. Patients' concerns should be understood and addressed. Those with prominent psychiatric disease may benefit from psychotherapy. Hypnotherapy benefits symptoms in those without psychologic disturbance, but its availability is limited. Antidepressants are effective in improving both mood and IBS symptoms globally, and the evidence is particularly good for tricyclic antidepressants. Although antispasmodics are currently the most commonly prescribed drugs, most responses (75%) are due to the placebo effect and not specific to the drug. Bulk laxatives such as ispaghula can increase stool frequency and help pain, but bloating may be aggravated. Loperamide is effective treatment for urgency and loose stools, but less effective for bloating and pain. 5-HT(3) antagonists such as alosetron improve urgency, stool consistency, and pain in diarrhea-predominant-IBS. The 5-HT(4) agonist tegaserod shows modest benefit in constipation-predominant IBS, improving stool frequency, consistency, and bloating as well as global improvement. There are many new drugs, such as cholecystokinin, neurokinin, and corticotropin receptor antagonists, in development."Gastroenterology. 2003 May;124(6):1662-71. Related Articles, Links Postinfectious irritable bowel syndrome.Spiller RC.Division of Gastroenterology, University Hospital, Nottingham, United Kingdom. robin.spiller###noittingham.ac.ukA small but significant subgroup of patients with irritable bowel syndrome (IBS) report a sudden onset of their IBS symptoms after a bout of gastroenteritis. Population-based surveys show that although a history of neurotic and psychologic disorders, pain-related diseases, and gastroenteritis are all risk factors for developing IBS, gastroenteritis is the most potent. More toxigenic organisms increase the risk 11-fold, as does an initial illness lasting more than 3 weeks. Hypochondriasis and adverse life events double the risk for postinfective (PI)-IBS and may account for the increased proportion of women who develop this syndrome. PI-IBS is associated with modest increases in mucosal T lymphocytes and serotonin-containing enteroendocrine cells. Animal models and some preliminary human data suggest this leads to excessive serotonin release from the mucosa. Both the histologic changes and symptoms in humans may last for many years with only 40% recovering over a 6-year follow-up. Celiac disease, microscopic colitis, lactose intolerance, early stage Crohn's disease, and bile salt malabsorption should be excluded, as should colon cancer in those over the age of 45 years or in those with a positive family history. Treatment with Loperamide, low-fiber diets, and bile salt- binding therapy may help some patients. Serotonin antagonists are logical treatments but have yet to be evaluated.Publication Types: Review Review, Tutorial PMID: 12761724and this was a comment from him when other doctors suggested"Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome."he respondedEditorialsNeuropathology of IBS?Robin C. Spiller [MEDLINE LOOKUP]
http://www2.us.elsevierhealth.com/scripts/...004857&nav=full and some of this information is from 2002 and they know more about it all since then and a lot of them all share resources and studies and peer reviews.hence theFrom - Report on the 5th International Symposium on Functional Gastrointestinal DisordersApril 4, 2003 to April 7, 2003 Milwaukee, Wisconsin By: Douglas A. Drossman, M.D ., UNC Center for Functional GI and Motility Disorders at Chapel Hill, and William F. Norton, IFFGDBasic Principles -- Brain-Gut Moderators: Emeran Mayer MD; Robin Spiller MD. Panel: Robin Spiller MD; Jackie Wood PhD; George Chrousos MD; Yvette Tach� PhD; Lisa Goehler PhD; G.F. Gebhart PhD; Emeran Mayer MD. Click on Titles to View Other TopicsIntroductionOutcomes of Pediatric Functional GI Disorders Epidemiology/Genetic/Behavioral Factors Brain Imaging Emerging Techniques to Evaluate and Treat Functional GI and Motility Disorders Clinical Applications of Diagnosis and Treatment Functional GI DisordersGeneral Principles of TreatmentPharmacological Treatment Psychological Treatment IFFGD Research AwardsThe brain-gut axis refers to the continuous back and forth interactions of information and feedback that take place between the gastrointestinal tract, and the brain and spinal cord (which together comprise the central nervous system). These interrelated feedback circuits can influence brain processes and bowel functions -- affecting pain perception, thoughts and one's appraisal of symptoms, gut sensitivity, secretions, inflammatory responses, and motility. The brain-gut circuits can be activated by an external or internal factor or stimulus that makes a demand on the system, such as a stressful event, an injury, an emotional thought or feeling, or even the ingestion of food. Symptoms of functional GI disorders may result from a maladaptive response to stimuli at some point within the complex interactions that take place along the brain-gut axis. Basic science is the fundamental approach to understanding how systems work. Basic research takes place in the laboratory and often involves the study of molecules and cells. From this body of knowledge is drawn the means to investigate practical applications and to formulate clinical practices. Translational science converts basic science discoveries into the practical applications that benefit people. One of the more exciting areas of recent research relates to the basic and translational aspects of the effects of stress on inflammation, cytokine and immune modulation, and pain. (Cytokines are a type of protein released by cells of the immune system, which act through specific cell receptors to regulate immune responses.) This series of presentations address three important research areas in the field of functional GI disorders, which have recently attracted considerable attention: the role of immune activation in the gut and the interactions of the gut immune and nervous systems; the role of the central nervous system in the regulation (modulation) of pain perception (nociception); and the emerging field of animal models with relevance for functional GI disorder research. This section demonstrates the rapid progress seen in the last few years in better understanding of basic mechanisms, in particular the neuroimmune interactions underlying symptom generation in patients with "functional" GI disorders. There are immune responses to infections. To defend itself from a foreign substance or invader, such as a bacterium or virus, the body mounts an immune response controlled by the brain. There needs to be a balance between infection and the body's immune response; the immune system needs to turn on and turn off at the right times to destroy the invader but not to the degree that it may harm healthy tissue. Robin Spiller, University Hospital, Nottingham, England began the session by noting the difficulty in separating disorders of structure ("organic") from disorders of function. He noted, "The difference is based on how high the power of your microscope is." This was elaborated upon in his presentation on Post-infectious Functional GI Disorders. It has been observed that IBS-like symptoms, that persist for 6 months to a year or longer, may appear after a bout with an acute infection in the gastrointestinal tract (e.g., food-poisoning). This is termed, "post-infectious IBS." A study by Gwee et al showed that the presence of unusual or amplified life stress at the time of onset of infection increased the chances of developing IBS symptoms. Inflammation persisted in patients with IBS-like symptoms but did not in patients whose symptoms resolved. This suggests that the brain's management of certain stressful stimuli (i.e., psychologic distress) affects the brain-gut system's ability to inhibit inflammation. It has frequently been observed that some individuals with more severe symptoms of IBS have coexisting psychologic distress. Stress has been thought to influence health-care seeking behavior, either by increasing motility, visceral hypersensitivity or inflammation, or by enhancing one's perception of gut symptoms, all of which lead to a greater need to seek care for them. The concept of post-infectious IBS suggests that in some circumstances stress (the biological process by which the body adapts in response to a stimuli) may influence symptoms. Persistence of the underlying inflammatory response may lead to post-infectious disorders of function. A variety of neuroimmune responses can lead to intestinal over-responsiveness (sensitization) and other clinical effects. These responses include direct toxicity to nerves that influence intestinal contractions, alteration in gut immune activation, abnormalities of serotonin metabolism, and persisting low-grade inflammation. IBS developing after infective gastroenteritis is associated with subtle increases in enteroendocrine and chronic inflammatory cells in the gut mucosa. The net effect may be to increase serotonin availability in the gut and enhance secretion and propulsive motility patterns. Serotonin antagonists may be beneficial in such patients Notably, the concept of "post-infectious IBS" has grown to include studies of their application in post-infectious gastroparesis and dyspepsia. 1Major inflammatory responses have not been observed in most IBS patients. However, in some studies subtle changes associated with inflammation have been noticed, such as increased presence of mast cells (a type of immune system cell present in blood and tissue). Jackie Wood, Ohio State University College of Medicine discussed the Effects of Inflammation on the Gut Enteric Nervous System, specifically noting the importance of mast cell degranulation (the release from within the cell of granules, or small sacs, containing chemicals that can digest microorganisms and fight infection). In tissue mast cells accumulate around nerve endings of nerves that contain the neurotransmitter serotonin. The release of substances that can induce activity in excitable tissue (i.e., histamine, Interleukin-1 (IL-1), and bradykinin) by mast cells can affect receptor and neurotransmitter function in the enteric nervous system - the part of the autonomic nervous system that controls function of the gastrointestinal tract. In other words, when mast cells in the intestinal lining empty their contents in response to an infection, they activate nearby nerve endings. In a subgroup of patients, this can have significance in terms of resulting clinical consequences of diarrhea and abdominal discomfort. 2----------------------------------------------side notehistimine is released in the gut by stress and effects mast cellsalso"Jack Wood, PhDProfessor of Physiology and Internal MedicineChairman Emeritus, Department of PhysiologyThe Ohio State University College of Medicine Dr. Wood was the first to use microelectrodes to record the electrical and synaptic behavior of neurons in the enteric nervous system. He coined the term "brain-in-the-gut" in view of emerging evidence that the enteric nervous system had neurophysiological properties like the brain and spinal cord. In recent years he has focused on signaling interactions between the enteric immune system and the brain-in-the-gut during infectious enteritis and food allergy. In this lecture he shows how the central nervous system, enteric nervous system and intestinal immune system are integrated during physical and emotional stress to produce irritable bowel symptoms of diarrhea and abdominal pain and discomfort. "
http://www.conference-cast.com/ibs/Lecture...dRegLecture.cfm -------------------------------------------------Yvette Tach�, University of California Los Angeles discussed Stress and Inflammation. The experience of stress is an adaptive behavior common to all living organisms. The activation of corticotropin releasing factor (CRF) signaling pathway, is the major mediating mechanism involved with the body's stress response system in which gastric emptying is inhibited (with possible loss of appetite) while colonic motor activity is stimulated (producing a loose stool or a sensation of bowel urgency). There is growing evidence that activation of this CRF pathways impacts on inflammation, autonomic nervous system function, immunity, and clinical behavior or illness, all of which may be linked to the pathophysiology of the functional gastrointestinal disorders. While we often talk about how the brain -- influenced for example by arousal and/or psychosocial factors -- can affect immune function, the reverse is also true. Immune activation, following infection for example, can influence brain function. Lisa Goehler, University of Virginia discussed Cytokines and Vagal Afferents: Immune Signaling to the Brain. Cytokines are substances that are produced by white blood cells to regulate certain functions during inflammatory and immune responses. The vagus is a nerve made of both sensory and motor fibers that innervates nearly every internal organ. The gastrointestinal (GI) tract, along with the lungs and liver, is an area of tissue that most commonly comes in contact with microorganisms (pathogens), such as bacteria or viruses, capable of activating an immune response. Cytokine mediators activate neurons that convey messages from tissue to the brain (afferent neurons) through the vagus nerve. The GI tract is richly supplied with vagal afferents that can signal immune activation in the tissue. This process may underlie the mechanism that causes individuals to feel sick. The concept of "sickness symptoms" is not always recognized. The cytokine inflammatory and immune mediators distributed throughout the body (peripheral), which appear to interact through vagal pathways, have systemic effects that manifest as symptoms in the body. (Mediators are substances released from cells to regulate immune responses.) Such symptoms include fever, increased sensitivity to pain, loss of appetite, and decreased desire for social interaction. The process may provide the basis for a role of the vagus as an interface between the site of the immune response and the brain that results in symptoms of altered mood, including anxiety or depression, that are sometimes associated with gastrointestinal disease. 4 Jerry Gebhart, The University of Iowa discussed the CNS Modulation of Visceral Nociceptive Responses. The central nervous system (CNS) is composed of the brain and spinal cord. The brain interprets and influences our perceptions of the pain sensation signals transmitted from the gut (visceral nociceptive responses) to the spinal cord and then to higher centers. Several structures in the brain (periaqueductal gray, dorsolateral pons, and rostroventral medulla) can facilitate or inhibit signals sent to the CNS and influence the perceived discomfort, or even whether the signals are experienced as pain. Inflammation of the bowel can produce increased sensitivity to pain or enhanced intensity of pain sensation (hyperalgesia) via increased activity of certain cells (for example, those that contain nNOS) in these higher brain modulatory centers. 5 To close the Brain-Gut sessions, Emeran Mayer, University of California Los Angeles discussed Evolving Animal Models of Visceral Hypersensitivity. In contrast to most other disorders of the digestive system, functional disorders of the gut continue to be defined by symptom criteria rather than by biological markers. Realistic animal models of functional gastrointestinal (GI) disorders in which to test hypotheses have not been available until recently. While it is unlikely that there will ever be an animal model to replicate all complexities of the human functional GI disorders, animal research is likely to help us understand some of the key underlying mechanisms responsible for symptom generation. This includes over-responsiveness of central stress circuits to visceral and psychological stimuli, resulting in altered autonomic responses (motility, secretion), increased pain sensitivity (visceral hypersensitivity) and possibly altered immune function of the gut. Future studies with genetically altered (i.e., transgenic) mice that become models for studying specific human diseases and their treatments may further increase our understanding of these mechanisms"
http://www.iffgd.org/symposium2003brain-gut.html From - Report on the 5th International Symposium onFunctional Gastrointestinal DisordersApril 4, 2003 to April 7, 2003 Milwaukee, Wisconsin By: Douglas A. Drossman, M.D., UNC Center for Functional GI and Motility Disorders at Chapel Hill, and William F. Norton, IFFGDBrain Imaging Moderator: Reza Shaker MD. Panel: Reza Shaker MD; Bruce Naliboff PhD; David Thompson MD. "Central activation -- the rapid short-term biophysical and biochemical changes in neurons that make possible such activities as thought, perception, and voluntary movement -- appears to increase as intensity of stimulus increases. However, repeated exposure can lead to adaptation, as the brain adjusts to the stimuli, with decreased central activation. In studies, IBS patients are differentiated from healthy controls by showing greater activation of an area of the brain essential for conscious pain (the anterior mid-cingulate component of the anterior cingulate cortex). It is in this region in the brain where the systems concerned with emotion or feeling, attention, and working memory interact. On the other hand, controls (and also patients with inflammatory bowel disease who have adapted to the visceral signals) show greater activation of the descending pain inhibitory pathways in areas of the brain involved in the suppression of pain (in the brain stem in the region of the periaqueductal gray). " From - Report on the 5th International Symposium onFunctional Gastrointestinal DisordersApril 4, 2003 to April 7, 2003 Milwaukee, Wisconsin By: Douglas A. Drossman, M.D., UNC Center for Functional GI and Motility Disorders at Chapel Hill, and William F. Norton, IFFGDEpidemiology/Genetic/Behavioral Factors This is very important also to the big picture.
http://www.iffgd.org/symposium2003factors.html ""But microscopic inflammation cannot be a diagnostic marker for IBS because it does not typically produce pain in those who have it."
