# Eric,anything new on distention sensitivity?



## SpAsMaN* (May 11, 2002)

Is it something scientifically proven?Why noboby is doing anything to help on this issue then?Is the rectal balloon distention is THAT different than normal people?


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## eric (Jul 8, 1999)

That is called viceral hypersensivity.This is new and I am still looking into it.It doesn't mean though anyone is making IBS up, its more technical then that in the details.IBS pain sensitivity may be psychological http://news.yahoo.com/s/nm/20070827/hl_nm/...chological_dc_1Centrally mediated is the central nervous system. This is is also new World J Gastroenterol. 2007 Jul 21;13(27):3699-704. LinksAbnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome.Wilder-Smith CH, Robert-Yap J.Brain-Gut Research Group, Bubenbergplatz 11, CH-3011 Berne, Switzerland. [email protected]: To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome (IBS). Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function. METHODS: Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities (visual analogue scale, VAS 0-100) during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously (heterotopic stimulation) were recorded in 40 female patients with IBS and 20 female healthy controls. RESULTS: Rectal hypersensitivity (defined by 95% CI of controls) was seen in 21 (53%), somatic hypersensitivity in 22 (55%) and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 (-11 to -1) in controls, but increased rectal pain by 2 (-3 to +6) in all IBS patients (P < 0.05) and by 8 (-2 to +19) in IBS patients with somatic and visceral hypersensitivity (P < 0.02). CONCLUSION: A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.PMID: 17659729


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## SpAsMaN* (May 11, 2002)

I don't know,i would rather buy the Permeability theoryr.Barbara.Mucosal Barrier Defects in Irritable Bowel Syndrome. Who Left the Door Open? http://www.blackwell-synergy.com/doi/abs/1...journalCode=ajg


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## eric (Jul 8, 1999)

Viceral hypersensivity has been demonstrated in IBS.Lower pain thresholds have been demonstrated in IBS and pain is a must for a diagnoses.Gut permeability is found not only in some IBSers, especially PI IBS, but other conditions. Stress itself can even cause it, so while an important part of research, its part of the wjhole picture. Dr Barb is an excellent researcher. You'll notice in her research the role of mast cells. They are also triggered from the stress system and are an important part of IBS research.Both the brain and the gut are operational to cause IBS symptoms, ts not a competition between the two, but how the two work and function together.For example I just posted this on another thread. Both EC cells and mast cells are important in IBS."FYI"You have two brains: one in your head and another in your gut. Dr. Jackie D. Wood is a renowned physiologist at The Ohio State University. He calls the second brain, "the-little-brain-in-the-gut." This enteric nervous system is part of the autonomic nervous system and contains over one hundred million neurons, which is as many as are in the spinal cord. This complex network of nerves lines the walls of the digestive tract form the esophagus all the way down to the colon. This little brain in the gut is connected to the big brain by the vagus nerves, bundles of nerve fibers running from the GI tract to the head. All neurotransmitters, such as serotonin that are found in the brain are also present in the gut.Dr Wood has discovered that this little-brain-in-the-gut has programs that are designed for our protection and which are very much like computer programs. They respond to perceived threats in the same way that the limbic system or the emotional brain does. So the threat of a gastrointestinal infection can activate the program that increases gut contractions in order to get rid of the infection. The symptoms are abdominal cramping and diarrhea. *Dr. Wood has determined that a type of cell found in the body and the gut, called the mast cell, is a key to understanding the connection of the big brain in the head with the little-brain-in-the-gut. Mast cells are involved in defense of the body. In response to certain threats or triggers, such as pollen or infection, mast cells release chemicals, such as histamine, that help to fight off the invader. Histamine is one of the chemicals that causes the symptoms of an allergy or a cold. When an infection of the gut occurs, such as food poisoning or gastroenteritis, the mast cells of the gut release histamine. The little-brain-in-the-gut interprets the mast cell signal of histamine release as a threat and calls up a protective program designed to remove the threat â€" at the expense of symptoms: abdominal pain and diarrhea. **The brain to mast cell connection has a direct clinical relevance for irritable bowel syndrome and other functional gastrointestinal syndromes. It implies a mechanism for linking allostasis and the good stress response to irritable states (e.g., abdominal pain and diarrhea) of the gut. Mast cells can be activated to release histamine in response to perceived psychological stress, whether the stressor or trigger is consciously perceived or not. So the end result is the same as if an infection activated the program in the-little-brain-in-the-gut: abdominal pain and diarrhea."*http://www.parkviewpub.com/nuggets/n5.html Chronic anxiety can also contribute to C as well. That is well known.Three mechansims contribute to IBS.MOTILITYIn healthy subjects, stress can increase motility in the esophagus, stomach, small and large intestine and colon. Abnormal motility can generate a variety of GI symptoms including vomiting, diarrhea, constipation, acute abdominal pain, and fecal incontinence. Functional GI patients have even greater increased motility in response to stressors in comparison to normal subjects. *While abnormal motility plays a vital role in understanding many of the functional GI disorders and their symptoms, it is not sufficient to explain reports of chronic or recurrent abdominal pain.* VISCERAL HYPERSENSITIVITYVisceral hypersensitivity helps to account for disorders associated with chronic or recurrent pain, which are not well correlated with changes in gastrointestinal motility, and in some cases, where motility disturbances do not exist. Patients suffering from visceral hypersensitivity have a lower pain threshold with balloon distension of the bowel or have increased sensitivity to even normal intestinal function. Additionally, there may be an increased or unusual area of somatic referral of visceral pain. Recently it has been concluded that visceral hypersensitivity may be induced in response to rectal or colonic distension in normal subjects, and to a greater degree, in persons with IBS. Therefore, it is possible that the pain of functional GI disorders may relate to sensitization resulting from chronic abnormal motor hyperactivity, GI infection, or trauma/injury to the viscera. http://www.med.unc.edu/ibsThe UNC Center for Functional GI& Motility Disorders5BRAIN-GUT AXISThe concept of brain-gut interactions brings together observations relating to motility and visceral hypersensitivity and their modulation by psychosocial factors. By integrating intestinal and CNS central nervous system activity, the brain-gut axis explains the symptoms relating to functional GI disorders. In other words, senses such as vision and smell, as well as enteroceptive information (i.e. emotion and thought) have the capability to affect gastrointestinal sensation, motility, secretion, and inflammation. Conversely, viscerotopic effects reciprocally affect central pain perception, mood, and behavior. For example, spontaneously induced contractions of the colon in rats leads to activation of the locus coeruleus in the pons, an area closely connected to pain and emotional centers in the brain. Jointly, the increased arousal or anxiety is associated with a decrease in the frequency of MMC activity of the small bowel possibly mediated by stress hormones in the brain. Based on these observations, it is no longer rational to try to discriminate whether physiological or psychological factors produce pain or other bowel symptoms. Instead, the Functional GI disorders are understood in terms of dysregulation of brain-gut function, and the task is to determine to what degree each is remediable. Therefore, a treatment approach consistent with the concept of brain-gut dysfunction may focus on the neuropeptides and receptors that are present in both enteric and central nervous systems. "http://216.109.125.130/search/cache?ei=UTF...=1&.intl=us


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## eric (Jul 8, 1999)

Spasman, it is something scientifically proven, but the exact causes are not completely understood.I did as Dr Drossman about this as well. I still need to look into it more however."I was also interested in Dr Whiteheads new study. From a general persons perceptive it kind of sounds like IBS is "all in the head" psychological when reading it, and I think some people reading that will look at it that way, but he really means I think and correct me if I am wrong, its more centrally mediated as in the brain gut connection and there is more to it in the details? I am interested on your thoughts on this, because I am trying to understand it better. Only if you have a minute on that though, I don't want to trouble you. With my own IBS I can get extremely severe pain. I did have PI IBS that developed into IBS when I was ten and had an extremely severe gastroenteritis from quite possibly coli in a swimming pool in Mexico that they said could have actually killed me."Reply, but he didn't have a lot of time yet on this. I might ask Dr Whitehead."That could be for another discussion. You are correct in your perception. It may have sounded like "all in the head" but that's not the best way to interpret/present it."Dr Drossman


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## eric (Jul 8, 1999)

SpasmanDr Barb was involved in thisTrends Pharmacol Sci. 2007 Aug 29; [Epub ahead of print]Novel therapeutic targets for enteric nervous system disorders.De Giorgio R, Barbara G, Furness JB, Tonini M.Department of Internal Medicine & Gastroenterology, University of Bologna, Bologna, Italy.There is a large unmet need for effective drugs for the treatment of gastrointestinal disorders, notably irritable bowel syndrome, functional dyspepsia and gastroesophageal reflux disease. The market value for an effective irritable bowel syndrome therapeutic agent is estimated at over US$10 billion per annum. *Each of these disorders seems to have a neural component*, involving the intrinsic innervation of the gastrointestinal system, its extrinsic innervation or both. The substantially improved understanding of the transmitters, receptors and ion channels of enteric neurons that now exists has led to targeted therapy. The most promising targets so far have been 5-hydroxytryptamine receptors. Other targets include opioid, cholecystokinin, tachykinin, cannabinoid, corticotropin-releasing factor and protease-activated receptors. Ion channels are also potential targets. Although current knowledge has yet to be adequately translated into effective therapies, each of the targets holds promise for the future that might be realized as new compounds with appropriate receptor specificity and pharmacodynamic profiles are developed.PMID: 17764756New Perspectives on Pathophysiology, Diagnosis, and Treatment -Douglas A. Drossman, MD http://www.expertinsightscme.com/pdf/ATxofIBS2006Part1.pdfalsoThe purpose of this research is to find out why IBS patients have abdominal pain. We were investigating whether the processing of pain in, and by, the brain, is different in these patients compared to healthy individuals. "Our studies have indicated that there may be a problem in certain centres of the brain, especially those pathways linking the emotional, cognitive and automatic nervous system responses of the brain, in people with IBS," said Prof Ho. Using an imaging tool to view the activation and deactivation of the brain centres involved in pain processing, the doctors found the two main brain areas associated with pain filter - namely, the emotional and cognitive processing areas - showed abnormal activation in IBS patients, but not in healthy individuals. Thus, people with IBS have a lower pain threshold because their pain filters appear to malfunction, amplifying rather than dampening the nervous input from the gut to the brain - resulting in a propensity for both abdominal pain, and an increased sensitivity to somatic (skin or surface) pain. "Compared to healthy subjects, IBS patients tend to have a more sensitive bowel. This can be explained by the finding that IBS sufferers have a lower pain threshold for perceiving abdominal pain, when compared to individuals who don't have IBS. "So, IBS patients may feel pain even when the intensity of a stimulation they receive is within a normal range," explained Prof Ho. http://www.channelnewsasia.com/stories/hea.../239806/1/.html1: J Clin Gastroenterol. 2006 Oct;40(9):814-20. Links Different Autonomic Responses to Experimental Pain in IBS Patients and Healthy Controls.Tousignant-Laflamme Y, Goffaux P, Bourgault P, Marchand S. Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada.BACKGROUND: Pain perception ratings in irritable bowel syndrome (IBS) patients suggest that they present either hypoalgesia or hyperalgesia. However, little is known about the physiologic responses these patients present to a somatic painful stimulus. GOALS: The main goal of this project was to study autonomic nervous system responses and the cardiac response to experimental pain in IBS patients. STUDY: This was addressed by exposing 27 women, 14 IBS, and 13 healthy controls (HCs), to a cold water (7 degrees C) immersion test of the forefoot for 2 minutes. Pain perception, galvanic skin responses (GSR), and heart rate (HR) were monitored during and after the immersion. RESULTS: For comparable pain perception, a significant group difference (P<0.02) in the cardiac response was observed during the immersion where the peak rise in HR was much higher for HCs, reaching 22%, whereas it only reached 8% for IBS patients. Moreover, HR variability analysis demonstrated that IBS and HCs had opposite autonomic cardiac reactivity to pain, where IBS had increased parasympathetic/decreased sympathetic reactivity. CONCLUSIONS: For comparable pain perception, IBS subject demonstrated different autonomic nervous system response to pain, *which supports the view of autonomic dysregulation in IBS.*PMID: 17016138 Histopathological alterations in irritable bowel syndrome.Mod Pathol. 2006 Sep 29; [Epub ahead of print] Links Histopathological alterations in irritable bowel syndrome.Kirsch RH, Riddell R. 1Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.Irritable bowel syndrome is a common disorder defined by a symptom complex including abdominal pain and altered bowel habit. The etiopathogenesis appears to be multifactorial and to involve altered gastrointestinal motor function, enhanced perception of visceral stimuli and psychosocial factors. More recently a role for mucosal immune activation has been suggested. Routine histologic examination reveals no mucosal abnormality in the majority of cases but quantitative histological, immunohistochemical and ultrastructural analyses reveal subtle morphologic changes involving lymphocytes, mast cells, enterochromaffin cells and enteric nerves. *The recent appreciation of these changes has led to new hypotheses linking central and enteric nervous systems to immune processes. *This review highlights the spectrum of morphologic changes that occur in irritable bowel syndrome, examines their relationship to the pathophysiology of irritable bowel syndrome and considers their relevance to daily pathology practice.Modern Pathology advance online publication, 29 September 2006; doi:10.1038/modpathol.3800704.PMID: 17013373 "Serotonin and Visceral HypersensitivityPatients with IBS may have an increased sensitivity to painful stimuli or an exaggerated response to normal stimuli, specifically in the colon and rectum,[4,49,50] but they do not demonstrate generalized hypersensitivity to painful somatic stimulation.[38] Studies have demonstrated that patients with IBS may perceive painful stimuli in the colon and rectum with a lower threshold than do individuals without this disorder. For instance, patients with IBS are more sensitive to balloon distention in the rectum (i.e., feel discomfort at lower levels of balloon inflation) than patients without IBS.[49,50] This concept, referred to as visceral hypersensitivity, may help explain the presence of abdominal pain or discomfort in patients with IBS.Other studies have demonstrated altered processing of brain signals. Patients with IBS may differ from patients without IBS in how their CNS integrates and processes signals from the gut.[4,50] For example, positron emission tomography, which can identify areas of increased brain blood flow in healthy controls, showed that colorectal distention activated the anterior cingulate cortex, an area rich in opiate receptors that may be involved in inhibiting painful sensations. However, this area was not activated in patients with IBS. Patients with IBS may process CNS information differently, and this processing may fail to activate brain areas involved in pain inhibition or the processing of painful stimuli.[38,51] In another study, functional magnetic resonance imaging showed that the anterior cingulate cortex was activated upon painful visceral stimulation both in patients with IBS and in controls, but that IBS patients had enhanced pain sensitivity and perception of visceral afferent (sensory) signals in the brain-gut axis corresponding to increased subjective reports of pain.[52]Serotonin may play a major role in the visceral hypersensitivity seen in patients with IBS.[50] 5-HT3-receptors transmit sensory information from the gut to the spinal cord.[4] Although the exact mechanism by which 5-HT4-receptors are involved in visceral sensation remains unknown, stimulation of 5-HT4-receptors has been shown to decrease the activity of the visceral afferent nerve fibers.[4,50,53,54] Peripheral 5-HT4-receptor-mediated mechanisms are thought to be involved in colonic hypersensitivity. Agonism of 5-HT4-receptors was shown to normalize pain sensitivity in an in vitro splanchnic nerve colon preparation from rats"http://www.medscape.com/viewarticle/503569_5There is a newer study I am looking for though. When I find that I will post it


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## eric (Jul 8, 1999)

FYINeuromuscular Dysfunction and IBS: Clinical Implications"Pathophysiology of IBSClassically, the pathophysiology of IBS has been thought to involve an interplay between psychosocial stressors and abnormalities in gut motility and visceral sensation. A variety of motility abnormalities have been described in IBS, including more frequent and prominent colonic contractions in response to meals in patients with IBS and diarrhea (IBS-D), and delayed colonic motility or abnormal colonic propulsive activity in patients with IBS and constipation (IBS-C).[1] Additionally, disorders of evacuation, as seen with puborectalis dysfunction or a rectocele, may also play a role, either alone or in conjunction with abnormal motility, in some IBS patients.Visceral hypersensitivity has long been accepted as an important feature in a subset of IBS patients and has even been suggested by some to be a biological marker of the condition.[2] Until recently, the concept of visceral hypersensitivity was based largely upon studies that identified differences in patient pain response or cortical activation measured by brain imaging techniques following painful visceral distention. An interesting recent study using functional magnetic resonance imaging (fMRI) found that subliminal rectal distention resulted in a greater volume of cortical activation in IBS patients than in controls. By eliminating the effects of stimulus-related cognitive processes through the use of subliminal stimuli, this study *more definitively established the hypersensitivity of neural circuitry involved in visceral sensation in IBS patients*.[3]"http://www.medscape.com/viewarticle/548600_1Advances in the Pathophysiology of IBS and Chronic ConstipationPosted 04/27/2006Michael D. Gershon, MD"IBS -- A Gastrointestinal or Psychiatric Disorder?The diagnosis of IBS involves a year's history of at least 12 weeks (not necessarily consecutive) of pain or abdominal discomfort that is relieved with defecation and/or is associated with a change in stool frequency and/or stool form.[1,17] Patients with IBS with diarrhea (IBS-D) have been reported to exhibit an increase in high-amplitude propagating contractions (HAPCs) and transit in the colon,[18,19] whereas those with IBS with constipation (IBS-C) may have reduced numbers of HAPCs and reduced transit.[19-21] *Most significantly, patients with IBS-D and IBS-C exhibit visceral hypersensitivity or allodynia.[*22-25] These observations suggest that the bowel is not functioning properly in IBS. Despite this suggestion, however, most physicians do not believe that IBS is primarily a gastrointestinal disease. Certainly, patients with IBS also suffer from a fair amount of associated psychopathology[24] as well as from dyspepsia, gastroesophageal reflux disease, and other problems of the upper gastrointestinal tract.[26]The frequent comorbidity of IBS with psychiatric disorders has been taken as evidence that IBS and psychiatric disorders share pathophysiologic mechanisms.[24] A common pathology at work in IBS and psychiatric disorders, even one that also affects the upper bowel and other organs, has tempted many physicians to assume that the comorbid psychiatric disorder is the cause of IBS, dyspepsia, fibromyalgia, and especially visceral hypersensitivity. Certainly, *functional brain imaging techniques suggest that central pain modulation circuits are altered in IBS, and the cortex is more responsive even to subliminal rectal stimuli.[24,25] Why central pain modulation circuits are altered, however, and whether their alteration is a result of aberrant input from the periphery, are still open to question."*"Sensory Transduction -- The Role of SerotoninTo regulate enteric behavior, it is necessary for conditions prevailing in the lumen of the bowel to be closely monitored by both the CNS and the ENS. Nerves, however, do not enter the lumen of the gut.[22] It therefore follows that sensory transduction from the lumen to primary afferent neurons, both intrinsic and extrinsic, is transepithelial. This process involves the very complex and extensive enteroendocrine cell system of the mucosal epithelium.[29,30] There are approximately 15 types of enteroendocrine cell, each of which is characterized by a unique secretory product. For example, G cells secrete gastrin, S cells secrete secretin, I cells secrete cholecystokinin, and enterochromaffin (EC) cells secrete serotonin (5-hydroxytryptamine [5-HT]).[31-35] Collectively, enteroendocrine cells all arise from endoderm-derived epithelial stem cells and secrete into the underlying lamina propria.[31,33] These cells undergo turnover and are in motion; therefore, there can be no fixed synapses between enteroendocrine cells and nerve fibers.The potential defect represented by the large gap between EC cells and their targets is overcome by the secretion of sufficient transmitter to flow to relatively distant afferent nerve processes of the mucosa. The downside of this massive transmitter release is that transmitter-removal mechanisms are critical. The EC cell is especially noteworthy with respect to gastrointestinal motility and IBS because 5-HT has been implicated in the signal transduction mechanism that initiates peristaltic and secretory reflexes and because drugs that affect 5-HT signaling have proven to be effective in preventing the nausea associated with cancer chemotherapy and in the treatment of IBS-D, IBS-C, and chronic constipation. EC cells produce and contain most of the body's 5-HT,[31] although significant amounts are also found in the ENS[22] and, of course, the CNS, where the effects of 5-HT are better known. The massive amount of 5-HT that is secreted reflects EC cell turnover and results in an overflow of 5-HT and metabolites into the lumen of the gut[36,37] and the portal circulation.[38] It has only recently become possible to detect the release of 5-HT from small numbers of EC cells in real time.[39]http://www.medscape.com/viewarticle/530404_2Mucosal Mast Cell Counts Correlate With Visceral Hypersensitivity in Patients With Diarrhea Predominant Irritable Bowel Syndromehttp://www.medscape.com/viewarticle/525166MEDLINE Abstracts: Serotonin Signaling and Visceral Hypersensitivity in IBShttp://www.medscape.com/viewarticle/462728IBS Patients Show Greater Brain Response to Subliminal Gut StimuliNEW YORK (Reuters Health) Feb 13 - A new study demonstrates that patients with irritable bowel syndrome (IBS) show greater sensitivity in their visceral sensory neural circuitry in response to subliminal stimuli than healthy controls.Tests for visceral hypersensitivity in IBS have relied on perceived stimulus, Dr. Reza Shaker and colleagues from the Medical College of Wisconsin and Milwaukee write in the January issue of Gastroenterology. Given that subliminal stimuli have recently been shown to register in the cerebral cortex, they add, it is now possible to evaluate gut neurocircuitry without the effect of cognitive processes.To test the hypothesis that IBS patients would show a greater response to subliminal stimuli of visceral neurocircuitry, the researchers evaluated fMRI activity in 10 IBS patients and 10 controls during rectal distension with a computerized, barostat-controlled device.Study participants were evaluated at 10, 15 and 20 mm Hg. Threshold for perception was 21 mm Hg in IBS patients and 25 in controls. All IBS patients showed cerebral cortical activity several times greater in volume in response to the same level of pressure as age- and sex-matched controls.The findings could be used to distinguish between neural and neurocognitive effects of IBS drugs, and also to stratify patients based on neural or neurocognitive abnormalities, the researchers write."The findings of this study also objectively show the existence of long-suspected neural hypersensitivity in IBS patients and as such help better dissect and define different pathophysiologic components that may exist in this patient group," they add.Questions remain about whether changes in IBS patients' visceral perception and autonomic response may be caused by emotional and cognitive factors that alter central pain modulation, Drs. Bruce D. Naliboff and Emeran A. Mayer of the David Geffen School of Medicine at the University of California, Los Angeles, write in an accompanying editorial. Another question is whether visceral hypersensitivity is specific to IBS or appears in other types of functional disorders as well.New, more sophisticated imaging and analysis techniques along with more specific study designs should help to answer these questions, the editorialists conclude.Gastroenterology 2006;130:26-33,267-269.Irritable Bowel Syndrome (IBS): Examining New Findings and Treatments







"Visceral hypersensitivity, CNS modulationPatients with IBS have increased sensitivity to visceral pain. Studies involving balloon distention of the rectosigmoid colon have shown that patients with IBS experience pain and bloating at pressures and volumes much lower than control subjects (12). These patients maintain normal perception of somatic stimuli. Multiple theories have been proposed to explain this phenomenon. For example, receptors in the viscera may have increased sensitivity in response to distention or intraluminal contents. Neurons in the dorsal horn of the spinal cord may have increased excitability. In addition, alteration in CNS processing of sensations may be involved (6). *Functional magnetic resonance imaging studies have recently shown that compared with control subjects, patients with IBS have increased activation of the anterior cingulate cortex, an important pain center, in response to a painful rectal stimulus *(13). http://www.postgradmed.com/issues/2002/11_02/morgan1.htmThere is still a newer one I am looking for that shows brain gut interactions and viceral hypersensvity. Its not that they don't know this, its that they are looking to see where all the problems are, in how the brain processes pain or in gut to brain neurotransmission which you have to have for pain or just the gut or just the brain, but right now its looking like how they communicate together and that problems can arise all along the brain gut axis. There are issues in both the gut and the brain in IBS. Looking at the enteric nervous sytem, the autonomic nervous system and the central nervous system and how they all inter-react together.


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## eric (Jul 8, 1999)

FYI"IBS: An anatomy of what goes wrong in the bodyAlthough the precise trigger of irritable bowel syndrome (IBS) remains unknown, researchers in the last decade have made substantial progress in understanding what goes awry in patients who suffer from the condition. Studies have shown that many IBS sufferers are hypersensitive to stimuli in the gut. Their brains process those stimuli differently, and many also have heightened gut-immune responses.As a result, researchers are beginning to look at IBS as an explainable disease rather than as a mysterious disorder. "As more of these abnormalities are being found in IBS, the distinction between a functional disorder and an organic disorder is being blurred," noted George F. Longstreth, MD, chief of gastroenterology at Kaiser Permanente Medical Care Program in San Diego.Researchers at the University of California, Los Angeles, for example, found that when they used an inflatable balloon to distend the rectum and lower colon of IBS patients, *PET scans of the brain showed greater activity in the brain's emotion and attention processing centers than in those of normal control subjects given the same stimulus. Those findings were confirmed by researchers at Vanderbilt University who used MRI studies instead of PET scans. *"Patients with IBS are hypervigilant," explained Brian Lacy, MD, director of the Marvin M. Schuster Center for Digestive and Motility Disorders at Johns Hopkins Bayview Medical Center in Baltimore. "They listen to their guts too carefully and hear every little contraction, gurgle and peristaltic wave."Other studies have shown that IBS patients have lower visceral pain thresholds and greater gut reactions to psychological stress than control subjects. Those data have led some to hypothesize that a visceral hypersensitivity causes many IBS symptoms.Whether that hypersensitivity originates in the brain or in the nervous system of the gut is unclear. Regardless of its origin, treatments that target the region of the brain shown to be hyperactive in IBS patients can effectively relieve symptoms. That's why therapies like cognitive behavioral therapy, alosetron, low-dose tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and cognitive therapy all work.Although abnormalities in brain processing are thought to play a role in IBS, researchers have also found how some symptoms stem from the actions of nerves in the gut. The role of the "gut-brain" connection has recently gained more prominence as researchers continue to uncover its extensive influence on bowel motility, secretion, immune responses and signaling to the central nervous system. Much of that influence gets carried out via the neurotransmitter serotonin. Remarkably, about 95% of the body's serotonin is found in the gut. Two serotonin receptor subtypes, 5-HT3 and 5-HT4, are thought to be responsible for the majority of the neurotransmitter's intestinal effects. It's no surprise, then, that alosetron and tegaserod, the first two drugs shown to affect the broad spectrum of IBS symptoms, target 5-HT3 and 4. SSRIs may also act on the bowel's nervous system, although they are thought to have a greater effect on the brain. There's also preliminary evidence that many IBS patients have a heightened immune response in the gut that includes a boosted number of mast cells, natural killer cells, lymphocytes and serotonin-laden enterochromaffin cells. Interestingly, between 10% and 30% of patients who recover from food poisoning develop IBS, especially if they were under undue psychological stress at the time they developed acute gastroenteritis."There's one theory that the infection and stress alter the permeability of the gut mucosa so that bacteria or viruses invade the gut where they don't belong," Dr. Lacy said. "This leads to chronic inflammation that could result in disordered motility and sensation by injuring nerves in the gut." The excessive numbers of enterochromaffin cells in some IBS patients could cause many IBS symptoms just by releasing their granules of serotonin."http://www.acponline.org/journals/news/sep03/ibs.htm#body


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## eric (Jul 8, 1999)

By the way spasman, you ask about inflammation. This is a part of it.Both the ec cell and the mast cells release serotonin, but the ec cell which stores the majority of serotonin in the gut realeases it to start gut contractions and in pain sensations and secreation. There seems to be a problem with its release from those cell receptors. The mast cell releases it to fight infections amoung other reasons. The mast cell also importantly releases histimine. This can be brought on by foods, stressors, both physical and mental and infection and some drugs. The system works on those issues to protect from any threat to the organism. The release from mast cells can contribute to pain in IBS. The release can cause tissue inflammation of the smooth muscle, but nothing like on the scale of IBD diseases.There is also a mast cell connection to bladder problems.Both cells are embbed in the gut wall and are in close proximity to each other.


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## SpAsMaN* (May 11, 2002)

Medscape:Hypersensitivity to Cutaneous Thermal Nociceptive Stimuli in Irritable Bowel SyndromeRodrigues AC, Nicholas Verne G, Schmidt S, Mauderli AP Pain. 2005;115(1-2):5-11OverviewIrritable bowel syndrome (IBS) is a common intestinal ailment affecting up to 20% of the US population.[1] It is one of the most frequent gastrointestinal disorders seen by physicians, comprising up to 50% of referrals to gastroenterologists and as many as 3.5 million visits to physicians each year in the United States.[2] The pathophysiologic mechanisms are not well understood. Most patients with IBS experience enhanced perception (visceral hypersensitivity) in response to distention of the gut lumen. But is this limited to their gut, or do they have a more general hypersensitivity to pain? The literature provides conflicting data.Rodrigues and colleagues shed light on the possible contribution of abnormal pain sensitization caused by positive feedback (vicious pain cycle) that affects somatic tissues. This results from a phenomenon called "viscero-somatic convergence." They used a temperature probe to measure cutaneous thermal pain sensitivity along the segmental axis, including dermatomes remote from the visceral pain focus (lower and upper extremities and the face) in 9 diarrhea-predominant IBS patients (diagnosed with ROME II criteria) and 12 healthy female controls.ResultsThese investigators found that in the participants with IBS, perception of sensitivity to heat was not limited to symptomatic dermatomes (calf) but extended evenly across the body, including to the face (no sensitization gradient from foot to face). Furthermore, the difference between IBS and control groups did not depend on the evoked pain-intensity level -- that is, the degree of sensitization of IBS patients was similar near threshold (10% on the visual analog scale) and at higher intensities. No correlation was found between the IBS patients' sensitivity to pain at any of the 3 test sites and their ratings of spontaneous pain.CommentaryPain sensitization of IBS patients is similar along the entire segmental axis and independent of the magnitude of disease-related spontaneous pain. These results can be interpreted as a pain sensitization or disinhibition phenomenon that is caused by a systemically or diffusely acting factor, not by a localized vicious cycle. These findings differ from those of an earlier IBS study that reported a higher degree of sensitization on the foot than on the hands[3] That study used a thermal stimulus consisting of hot water immersion of hand and foot, not a small area probe.It appears that the exaggerated sensitivity of IBS patients is specific to certain stimulus characteristics: Sensitization has been demonstrated with nociceptive hot[3] and nociceptive cold[4] but not with electrical[5,6] or uncomfortable yet nonpainful cold[7] stimuli to the skin. This stimulus-specificity argues against the notion that a mere rating bias or hypervigilance explains the higher-intensity ratings of stimuli by IBS patients compared with healthy individuals. The fact that ratings of visceral and cutaneous stimuli return to normal when IBS patients are treated with rectal lidocaine[8] or systemic fentanyl[9] further suggests that the higher ratings of IBS patients are not the result of a nonspecific shift in rating bias but instead are the result of pain sensitization.ReferencesVerne GN, Cerda JJ. Irritable bowel syndrome. Streamlining the diagnosis. Postgrad Med. 1997;102:197-198, 201-204, 207-208.Sandler RS. Epidemiology of irritable bowel syndrome in the United States. Gastroenterology. 1990;99:409-415.Verne GN, Robinson ME, Price DD. Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Pain. 2001;93:7-14.Bouin M, Meunier P, Riberdy-Poitras M, Poitras P. Pain hypersensitivity in patients with functional gastrointestinal disorders: a gastrointestinal-specific defect or a general systemic condition? Dig Dis Sci. 2001;46:2542-2548.Accarino AM, Azpiroz F, Malagelada JR. Selective dysfunction of mechanosensitive intestinal afferents in irritable bowel syndrome. Gastroenterology. 1995;108:636-643.Cook IJ, van Eeden A, Collins SM. Patients with irritable bowel syndrome have greater pain tolerance than normal subjects. Gastroenterology. 1987;93:727-733.Zighelboim J, Talley NJ, Phillips SF, et al. Visceral perception in irritable bowel syndrome. Rectal and gastric responses to distension and serotonin type 3 antagonism. Dig Dis Sci. 1995;40:819-827.Verne GN, Robinson ME, Vase L, Price DD. Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients. Pain. 2003;105:223-230.Lembo T, Naliboff BD, Matin K, et al. Irritable bowel syndrome patients show altered sensitivity to exogenous opioids. Pain. 2000;87:137-147. --------------------------------------------------------------------------------


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## SpAsMaN* (May 11, 2002)

OK Eric,now i need feedback from Doug on this:*Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients*http://cat.inist.fr/?aModele=afficheN&cpsidt=15143945Auteur(s) / Author(s)VERNE G. Nicholas (1) ; ROBINSON Michael E. (2) ; VASE Lene (2) ; PRICE Donald D. (3) ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)(1) Makom Randall VAMC, Research Service (151), 1601 SW Archer Road, Gainesville, FL 32608-1197, ETATS-UNIS(2) Clinical and Health Psychology, University of Florida College of Medicine, Gainesville, FL, ETATS-UNIS(3) Department of Oral & Maxillofacial Surgery, University of Florida College of Medicine, Gainesville, FL, ETATS-UNISRésumé / AbstractIrritable bowel syndrome (IBS) is one of the most common gastrointestinal illnesses and is characterized by altered visceral perception. The aim of the study was to determine if local anesthetic blockade of peripheral visceral nociceptive input reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. Ten women with IBS (mean age 30 ± 10 years) and ten control subjects (all women) (mean age 29 ± 7 years) rated pain intensity and unpleasantness to distension of the rectum (35 mmHg) and thermal stimulation (47 °C) of the foot before and after rectal administration of either lidocaine jelly or saline jelly in a double blind crossover design. Intrarectal lidocaine (300 mg) reduced reported rectal and cutaneous pain in all of the IBS patients. The effects were statistically much greater than those of placebo and most of the effects were present within 5-15 min after the onset of the treatment. In the control subjects, rectal lidocaine did not decrease pain report from visceral and cutaneous stimuli. The results of this study support the hypothesis that local anesthetic blockade of peripheral impulse input from the rectum/colon reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. The results provide further evidence that visceral hyperalgesia and secondary cutaneous hyperalgesia in IBS reflects central sensitization mechanisms that are dynamically maintained by tonic impulse input from the rectum/colon. *Rectal administration of lidocaine jelly may also be a safe and effective means of reducing pain symptoms in IBS patients.*Revue / Journal TitlePain (Pain) ISSN 0304-3959 CODEN PAINDB Source / Source


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## SpAsMaN* (May 11, 2002)

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## SpAsMaN* (May 11, 2002)

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## SpAsMaN* (May 11, 2002)

Damn,i'm not sure it would help.I just read few pages about a study.See for yourself but i'm still curious to try it:http://64.233.167.104/search?q=cache:x-HQz...cd=10&gl=ca


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## eric (Jul 8, 1999)

One of the studies you posted is looking at pain and IBS to see if pain is processed wrong in the whole body or localized to viceral hypersensivity.Also lidocaine jelly is a topical anesthesia used on the rectum for rectal hypersensivity. A Lot of IBSers have been shown to have rectal hypersensivity. This is still something the rectum that sends signals to the brain. In a way the rectum can start the pain ball in motion. This part"in IBS reflects central sensitization mechanisms" means in part the CNS mediated. alsoThere are two parts here, EC cells and serotonin and Mast cells, both contributing to the symptoms.Med Clin (Barc). 2007 Jun 9;129(2):61-9. LinksStress-mast cell axis and regulation of gut mucosal inflammation: from intestinal health to an irritable bowel. Article in SpanishRamos L, Vicario M, Santos J.Unidad de Investigación en Enfermedades Digestivas. Servicio de Aparato Digestivo. Hospital Universitari Vall d'Hebron. Departamento de Medicina. Universitat Autònoma de Barcelona. Barcelona. España.The functional gastrointestinal disorders and the irritable bowel syndrome, in particular, represent one of the commonest causes of medical consultation and the most frequent diagnosis raised by the gastroenterologists. Despite their high prevalence, the aetiology and pathophysiology of these functional digestive disorders remains unclear and specific diagnostic markers and clearly effective therapeutic options are lacking as well. These factors generate an important impairment in the quality of life in these patients and a growing sanitary burden. Recent studies showing the presence of low grade intestinal mucosal inflammation along with mast cell hyperplasia may contribute to the development and perpetuation of visceral hypersensitivity and dismotility patterns and epithelial barrier abnormalities, characteristic of the irritable bowel syndrome. In this article we will review the role of the stress-mast cell axis in the modulation of the gut mucosal inflammation and in the pathophysiology of the irritable bowel syndrome.PMID: 17588364 Now you remember this from the world expert Dr Wood? He is an expert on food allergies as well as the enteric nervous system or brain in the gut.You have two brains: one in your head and another in your gut. Dr. Jackie D. Wood is a renowned physiologist at The Ohio State University. He calls the second brain, "the-little-brain-in-the-gut." This enteric nervous system is part of the autonomic nervous system and contains over one hundred million neurons, which is as many as are in the spinal cord. This complex network of nerves lines the walls of the digestive tract form the esophagus all the way down to the colon. *This little brain in the gut is connected to the big brain by the vagus nerves, bundles of nerve fibers running from the GI tract to the head. All neurotransmitters, such as serotonin that are found in the brain are also present in the gut.*Dr Wood has discovered that this little-brain-in-the-gut has programs that are designed for our protection and which are very much like computer programs. *They respond to perceived threats in the same way that the limbic system or the emotional brain does. So the threat of a gastrointestinal infection can activate the program that increases gut contractions in order to get rid of the infection. The symptoms are abdominal cramping and diarrhea. **Dr. Wood has determined that a type of cell found in the body and the gut, called the mast cell, is a key to understanding the connection of the big brain in the head with the little-brain-in-the-gut. Mast cells are involved in defense of the body. In response to certain threats or triggers, such as pollen or infection, mast cells release chemicals, such as histamine, that help to fight off the invader. Histamine is one of the chemicals that causes the symptoms of an allergy or a cold. When an infection of the gut occurs, such as food poisoning or gastroenteritis, the mast cells of the gut release histamine. The little-brain-in-the-gut interprets the mast cell signal of histamine release as a threat and calls up a protective program designed to remove the threat â€" at the expense of symptoms: abdominal pain and diarrhea. **The brain to mast cell connection has a direct clinical relevance for irritable bowel syndrome and other functional gastrointestinal syndromes. It implies a mechanism for linking allostasis and the good stress response to irritable states (e.g., abdominal pain and diarrhea) of the gut. Mast cells can be activated to release histamine in response to perceived psychological stress, whether the stressor or trigger is consciously perceived or not. So the end result is the same as if an infection activated the program in the-little-brain-in-the-gut: abdominal pain and diarrhea."*http://www.parkviewpub.com/nuggets/n5.html


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## eric (Jul 8, 1999)

When the colon wall expands and contracts pressure sensitive cells releases neurotransmitters, importantly serotonin to intiate contractions. This is also communicating sensations to the brain. Another aspect of this is the sympathetic and parasympathetic nervous systems.Neuroimaging is a relatively new science.Neuroimaging has provided evidence of physiological differences between normal individualsand those suffering from IBS in the way a visceral stimulus (ie, rectal distention) is processed inthe brain.[14,15] Initial data from positron emission tomography (PET) scans demonstratedincreased activation of the anterior cingulate cortex (ACC) among normal individuals, comparedto IBS patients. The ACC is a cerebral cortical area that is rich in opiate receptors and is thoughtto be a major component of cognitive circuits relating to perception as well as descending spinalpathways involving pain. More recently, fMRI was used to demonstrate increased activity in theACC, prefrontal (PF), and insular cortex areas, and in the thalamus of IBS patients compared tonormal individuals."














One of these is using fmri and the other pet scans.It should be noted there is a difference between normals and IBS, but also a difference between IBD conditions and IBS. That is important in differences of inflammation and pain.Inflammation doesn't always cause pain for one, butIrritable Bowel Syndrome: How Far Do You Go in the Workup?"For example, there is a subgroup of patients, called "post-infectious IBS' who appear to respond to an enteric infection such as cawpylobactor jejuni with an increased inflammatory cell response.22This 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,*23But microscopic inflammation cannot be a diagnostic marker for IBS because it does nor 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 with patients with IBS seem to have higher pain thresholds.24In 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 pain inhibition systems that lead to the perception of pain and produce other symptoms that typify this disorder*.25In one prospective study of postinfectious IBS, it was found that those who retained their symptoms 3 months after an enteric infection had not only increased inflammation in the intestinal lining, but also had increased psychosocial distress at the time of the infection. Furthermore, lowered visceral pain thresholds and increased motility were present after the infection regardless of whether or not the patients retained their symptoms.*26Therefore, the microscopic inflammation and its physiologic effects on motility and sensation contribute to, but are not always sufficient for, the clinical expression of IBS pain. *http://216.109.125.130/search/cache?ei=UTF...=1&.intl=us


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## eric (Jul 8, 1999)

spasmanEvaluation of Visceral Sensation in IBS Patients Using Subliminal Stimulation"From Medscape GastroenterologyLiterature Review -- Select Topics in IBS and Chronic ConstipationLatest From the Literature in IBS and Chronic Constipation: September 2006Posted 09/07/2006Brian E. Lacy, MD, PhD IntroductionIn this second installment in our quarterly literature review series on topical issues in irritable bowel syndrome (IBS) and chronic constipation, 3 original research studies are reviewed. These reports describe new information regarding the pathophysiology of IBS, the role of alternative therapies in the treatment of IBS, and the treatment of constipation.""Lawal A, Kern M, Sidhu H, Hofmann C, Shaker R. Novel evidence for hypersensitivity of visceral sensory neural circuitry in irritable bowel syndrome patients. Gastroenterology. 2006;130:26-33.The pathophysiology of IBS involves multiple underlying factors, including abnormalities in visceral sensation, disturbances in gut motility, and differences in the central nervous system (CNS) processing of visceral pain.[1] Many investigators now believe that visceral hypersensitivity is the most important pathophysiologic abnormality in IBS patients. The mechanism that leads to visceral hypersensitivity in patients with IBS is unknown, although current theories postulate the presence of abnormal sensory receptors and sensory afferents, deficient descending modulating factors, and a hypervigilant CNS. This latter component has been demonstrated in studies using functional magnetic resonance imaging (fMRI) and positron emission tomography scans.[2,3] The end result is that IBS patients sense abdominal discomfort at lower levels than normal individuals and* often misinterpret normal sensations as painful (allodynia).[4] This has been demonstrated in a number of studies that typically involve distending the lumen of the gastrointestinal tract with a balloon*.[5] One concern is that these studies may be influenced by cognitive processes associated with perceived sensory stimulation. Stated another way, anticipation of a possibly unpleasant sensation (balloon distention of the rectum) may alter cortical activity and thus change fMRI findings. Lawal and colleagues[6] addressed this potentially confounding factor by evaluating visceral sensation in IBS patients using subliminal stimulation."*"This well-designed, novel study is the first to show that very low levels of distention in the gastrointestinal tract, without any related cognitive processes typically associated with perceived distention, lead to increased CNS activity in IBS patients compared with healthy volunteers. In addition, patients with IBS demonstrated a maximum response to subliminal distention, as compared with the graded response seen in healthy volunteers. These findings are important for a number of reasons. One, it confirms the now widely accepted view that the brain-gut axis is a critical component in IBS. Two, it emphasizes that hypersensitivity is a key underlying pathophysiologic mechanism in the generation of symptoms in IBS patients. And finally, although not evaluated in this study, these findings point out that therapeutic options for patients with IBS should focus on treating both the hypersensitive gut and the hypersensitive CNS."*http://www.medscape.com/viewarticle/544018_2


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## eric (Jul 8, 1999)

I was concerned when this first came out and emailed Dr Drossman on this and he said there would be info out on it all. IT does not mean we make it up though, its a lot more complx then that as you can see.It is also good to know these doctors work at different centers but respect each other and are basically all working together on common goals. UCLA is studying the brain and UNC is studying the gut, through NIH grants, but basically all IBS and other functional disorders and pain disorders and they share information. This is new commentary on the study and to me at least very interesting. "Increased colonic pain sensitivity in IBS is the result of an increased tendency to report pain rather than increased neurosensory sensitivity" was reported by Reuters, the world's largest international multimedia news agency, under the headline, "Pain sensitivity in IBS patients may be psychological." But is this interpretation correct; and if not, how should we interpret these findings?http://www.aboutibs.org:80/site/news-events/news/commentary


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## SpAsMaN* (May 11, 2002)

Eric,my feeling is pain should be adress locally.Pelvic pain can have numerous origin.It makes sense to find the source of it and trying to eliminate it.Chronic localized pain can exist with our without IBS.I mean distention could just exacerbate the irritation.


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## eric (Jul 8, 1999)

Spasman"Eric,my feeling is pain should be adress locally."Your missing some really important aspects to all this.All pain is processed in the brain. Is that locally? Or the singals to the brain? Or the is the brain processing those signals wrong? Can things that modify the signals help IBSers? So targeting the gut is one aspect of treating IBS, but treating the whole person gut and brain is showing better results in helping IBSers, especially moderate to severe IBS. This is basically psychophysiological and physiological. Anxiety and even emotions can trigger the underlying IBS and cause pain and symptoms, hence why you can help treat that aspect of the disorder, even though IBS is REAL and NOT IN THE HEAD or MADE UP.Its not everytime the word psychological is mentioned it means its all in the head and were crazy, that is not the case at all.with permissionI posting all of this because its important.The UNC Center for Functional GI http://www.med.unc.edu/ibs& Motility Disorders History of Functional DisordersDouglas A. Drossman, MDCenter-Co-DirectorMelissa Swantkowski New York UniversityTHE PASTHISTORICAL PRECEDENTSHistorians and physicians have documented the presence of Functional GI disorders throughoutrecorded human history. However, until recently, limited attention has been granted to thesedisorders due to the lack of identifiable pathology and the absence of a conceptual framework tounderstand and categorize them. Systematic investigation of functional GI disorders did notbegin until the middle of the 20th century, and prior to this time, only occasional reports offunctional GI symptoms were published, the first appearing only 200 years agver the past 25 years, scientific attention to understanding and properly caring for patients withfunctional GI disorders has grown progressively. With the understanding comes the rationale foruse of medications directed at intestinal receptors as well as psychopharmacological, behavioral,and psychological forms of treatment. Additionally, there has been an increase in the rate ofscientific publications and greater media exposure to the public through television, radio, andInternet.*To understand the historical classification of these disorders, two differing theories relating to theinteraction between the mind and body should be considered.o Holism: a theory built upon the foundation that the mind and body are integratedand utterly inseparable.o Dualism: a theory that proposes a separation between the mind and the body.*Greek philosophers Plato, Aristotle, and Hippocrates first proposed the principleof holism about 3,000 years ago, and later in the 12th century; Jewish physicianand philosopher Maimonides reexamined this philosophy. *Based on holism, thestudy of medical disease must take into account the whole person rather thanmerely the diseased part.* However, societal concepts of illness and diseasedrastically shifted when European philosopher Rene Descartes offered the divergent theory ofdualism in the 17th century. Prior to the notion of dualism, the church discouraged humandissection on the premise that the spirit resided in the body. The acceptance of dualism paved theway for the emergence of scientific investigation and new medical discoveries by lifting theprohibition of human dissection. This shift in medical thought was congruent with the societalchanges of the 17th century: the shift towards a separation in church and state.IMPLICATIONS FOR FUNCTIONAL GI DISORDERS*Based on the concept of dualism, disease was now understood in terms of structuralabnormalities. Therefore, the validity of a disease rested with the observation of morphologicalabnormalities. Medical conditions occurring in the absence of such morphological abnormalitiesand symptoms were not considered legitimate, and were often viewed as psychiatric, consistentwith the concept of dualism. The concept of dualism had other effects with regard to treatment.For example, this would include all the functional GI disorders and other somatic syndromes,such as fibromyalgia. Until the latter part of the 20th century, a medical illness was consideredamenable to scientific inquiry and treatment. However, patients with psychiatric disorders wereinterred in insane asylums and considered to no longer be treatable by medical physicians.Unfortunately this concept leads to a clinical dilemma. Specific diseases explain only about 10%of medical illnesses seen by physicians. Furthermore, people with structural (i.e. organic)diagnosis such as inflammatory bowel disease or cancer show considerable variation in theirsymptom presentation and clinical behavior. Gastroenterologists (as well as other health carepractitioners) are all too familiar with the poor correlation between structural findings onendoscopy and their patient's symptoms.**Although efforts to find morphological or even motility etiologies for functional GI disorders inthe latter part of the 20th century were unsuccessful, the assumption that functional GI disordersmust be psychiatric has developed and has permeated current thinking. However, in the face ofcurrent scientific research, this is being seriously challenged. Studies have shown that personswith irritable bowel syndrome who do not seek health care are psychologically much like healthysubjects.*THE PRESENTCONCEPTUAL BASES FOR THE STUDY OF FUNCTIONAL GI DISORDERSo The recent acceptance of functional GI disorders as legitimate medical entities isbased on the following three developments The concept of the Biopsychosocial model of illness and diseaseo The development of new investigative methods for studying diseaseo The development of the Rome CriteriaBiopsychosocial ModelIn 1977, the publication of the concept of the Biopsychosocial model by George Engel, and itslater demonstration specifically for gastrointestinal disorders, marked an important change inthinking. *A biopsychosocial model of illness and disease provides the needed framework tounderstand, categorize, and treat common GI symptoms. These symptoms are the integratedproduct of altered motility, enhanced visceral sensitivity, and brain-gut dysregulation and oftenare influenced by psychosocial factors.* Figure 1 illustrates the proposed relationship betweenpsychosocial and physiological factors with functional GI symptoms and the clinical outcome.Early in life, genetics and environmental influences (family attitudes toward bowel training orillness in general, major loss or abuse history or exposure to infection) may affect one'spsychosocial development (susceptibility to life stress, psychological state, coping skills, socialsupport) or the development of gut dysfunction (abnormal motility or visceral hypersensitivity).Additionally, the presence and nature of a functional GI disorder is determined by the interactionof psychosocial factors and altered physiology via the brain-gut axis. *In other words, oneindividual afflicted with a bowel disorder but with no psychosocial disturbances, good copingskills and adequate social support may have less severe symptoms and not seek medical care.Another having similar symptoms but with coexistent psychosocial disturbance, high life stress,or poor coping skills may frequent his physician's office and have generally poor outcome.*DEVELOPMENT OF NEW INVESTIGATIVE METHODSThe second concurrent process has been the expansion and refinement of investigative methodsthat allow the study of functional GI disorders in terms of biological, cultural, and psychosocial(i.e. brain) influences. These developments include:1. the improvement of motility assessment,2. the standardization of the barostat to measure visceral sensitivity,3. the enhancement of psychometric instruments to determine psychosocialinfluences,4. the introduction of brain imaging (PET, fMRI) to determine CNS contribution tosymptoms, and5. the molecular investigation of brain-gut peptides, which provide insight into howthese symptoms become manifest.In less than ten years, these methods have produced new knowledge of the underlyingpathophysiological features that characterize the age-old symptoms we now define as functionalGI disorders.ROME CRITERIAThe Rome Criteria is an international effort to characterize and classify the functional GIdisorders using a symptom-based classification system. This approach that has its precedentswith classification systems in psychiatry and rheumatology. The rationale for such a system isbased on the premise that patients with functional GI complaints consistently report symptomsthat breed true in their clinical features, yet cannot be classified by any existing structural,physiological or biochemical substrate. The Rome Criteria was built upon the Manning Criteria,which was developed from discriminate function analysis of GI patients.The decision to develop diagnostic criteria by international consensus was introduced as part of alarger effort to address issues within gastroenterology that are not easily resolved by usualscientific inquiry or literary review. By 1992, several committees had met to discuss the criteria,which ultimately resulted in the publishing of many articles in Gastroenterology Internationaland a book detailing the criteria titled "The Functional Gastrointestinal Disorders (Rome I)".Elaboration of the Rome I criteria led to a second edition of the Rome criteria (titled Rome II) in2000 as well as the publication of a supplement to the journal Gut in 1999. Recently the RomeCoordinating Committee has met to begin Rome III, expected to be published in 2006. To learnmore about the Rome Committees and to see a summary of the Rome II book: go towww.romecriteria.com.PRESENT PATHOPHYSIOLOGICAL OBSERVATIONSDespite differences among the functional gastrointestinal disorders, in location and symptomfeatures, common characteristics are shared with regard to motor and sensory physiology,o central nervous system relationships,o approach to patient care.What follows are the general observations and guidelines.MOTILITYIn healthy subjects, stress can increase motility in the esophagus, stomach, small and largeintestine and colon. Abnormal motility can generate a variety of GI symptoms includingvomiting, diarrhea, constipation, acute abdominal pain, and fecal incontinence. Functional GIpatients have even greater increased motility in response to stressors in comparison to normalsubjects. *While abnormal motility plays a vital role in understanding many of the functional GIdisorders and their symptoms, it is not sufficient to explain reports of chronic or recurrentabdominal pain.*VISCERAL HYPERSENSITIVITY*Visceral hypersensitivity helps to account for disorders associated with chronic or recurrent pain,which are not well correlated with changes in gastrointestinal motility, and in some cases, wheremotility disturbances do not exist.* Patients suffering from visceral hypersensitivity have a lowerpain threshold with balloon distension of the bowel or have increased sensitivity to even normalintestinal function. Additionally, there may be an increased or unusual area of somatic referral ofvisceral pain. Recently it has been concluded that visceral hypersensitivity may be induced inresponse to rectal or colonic distension in normal subjects, and to a greater degree, in personswith IBS. Therefore, it is possible that the pain of functional GI disorders may relate tosensitization resulting from chronic abnormal motor hyperactivity, GI infection, or trauma/injuryto the viscera.BRAIN-GUT AXIS*The concept of brain-gut interactions brings together observations relating to motility andvisceral hypersensitivity and their modulation by psychosocial factors. By integrating intestinaland CNS central nervous system activity, the brain-gut axis explains the symptoms relating tofunctional GI disorders. In other words, senses such as vision and smell, as well as enteroceptiveinformation (i.e. emotion and thought) have the capability to affect gastrointestinal sensation,motility, secretion, and inflammation. Conversely, viscerotopic effects reciprocally affect centralpain perception, mood, and behavior.* For example, spontaneously induced contractions of thecolon in rats leads to activation of the locus coeruleus in the pons, an area closely connected topain and emotional centers in the brain. Jointly, the increased arousal or anxiety is associatedwith a decrease in the frequency of MMC activity of the small bowel possibly mediated by stresshormones in the brain. Based on these observations, it is no longer rational to try to discriminatewhether physiological or psychological factors produce pain or other bowel symptoms. Instead,the Functional GI disorders are understood in terms of dysregulation of brain-gut function, andthe task is to determine to what degree each is remediable. Therefore, a treatment approachconsistent with the concept of brain-gut dysfunction may focus on the neuropeptides andreceptors that are present in both enteric and central nervous systems.THE ROLE FOR PSYCHOLOGICAL FACTORS*Although psychological factors do not define these disorders and are not required for diagnosis,they are important modulators of the patient's experience and ultimately, the clinical outcome.*Research on the psychosocial aspects of patients with functional GI disorders yields three generalobservations Psychological stress exacerbates gastrointestinal symptoms in patients withfunctional GI disorders and can even produce symptoms in healthy patients (but toa lesser degree).o Psychological disturbances modify the experience of illness and illness behaviorssuch as health care seeking. For example, a history of major psychological trauma(e.g. sexual or physical abuse) is more common among patients seen in referralcenters than in primary care and is associated with a more severe disorder and apoorer clinical outcome. Additionally, psychological trauma may increase painreportingtendency.o Having a functional GI disorder has psychological consequences in terms of one'sgeneral well-being, daily functional status, concerns relating to control oversymptoms, and future implications of the illness (e.g. functioning at work andhome).APPROACH TO TREATMENTThe approach to treatment for all functional GI disorders is founded on a therapeutic physicianpatientrelationship. The basis for implementing a strong physician-patient relationship issupported by evidence that patients with functional GI disorders have anywhere from a 30 to80% placebo response rate regardless of treatment.Because functional GI disorders are chronic, it is important to determine the immediate reasonsbehind each visit, after which treatment can be based on severity and nature of symptoms,physiological and psychosocial determinants of the patient's illness behavior, and the degree offunctional impairment.These factors can separate patients into mild, moderate, and severe categories.Patients with mild symptoms usually seen in primary care,o do not have major impairment in function or psychological disturbance ando can maintain normal activity.These patients have concerns about their condition but do not need to make many visits to theirphysician. Regarding treatment, these patients require education about their disorder and itssymptoms as well as information regarding a proper diet and the kinds of medication that canhave adverse effects.Patients with moderate symptoms seen in both primary and secondary care facilities ando experience intermittent disruptions in activity on account of their symptoms.o may identify a close relationship between symptoms and inciting events such asstress, travel, or dietary indiscretion.For these patients, symptom monitoring to record time, severity, and presence of associatedfactors can help to identify inciting factors and give the patient a sense of control over thedisorder. Additionally, pharmacotherapy directed at specific symptoms, particularly those thatimpair daily function, can be helpful, as can psychological treatments (relaxation, hypnosis,cognitive-behavioral therapy, and combination treatments) in reducing anxiety and encouraginghealth promoting behaviors.Patients with severe symptoms have trouble functioning daily,o find their disorder to be disabling and debilitating in nearly every facet of life,o have a high frequency of associated psychological difficulties,o make frequent visits to their physicians , ando may hope for a magical cure.In these cases a long-term physician-patient relationship, which sets realistic treatment goals(such as improved quality of life rather than elimination of all pain) is necessary. The focus forthese patients needs to shift from treating a disease to coping with a chronic disorder, wheremuch of the responsibility is place on the patient, himself. Furthermore, antidepressants haveproven useful to control pain and alleviate associated depressive symptoms.THE FUTUREFuture studies will identify pathophysiological subgroups, each having its own set ofdeterminants ad treatment. Examples are as follows Some patients will develop their disorders or exacerbate symptoms viasensitization of afferent transmission from infection, enhanced motility, or traumato the gut. They may respond to the newly developing neurotransmitter blockingagents.o Patients with more painful and severe symptoms may prove to have "abnormalperception of normal gut function" rather than abnormal function. Thisdysfunction in the central regulation of incoming visceral signs may be remediedwith a psychopharmacological treatment approach.o The symptoms of some patients could be attributed to genetic factors, which resultin abnormalities in central reactivity to stress, in which case genetic manipulationstrategies would prove beneficial.o Early learning within the familial structure and socio-cultural influences has beendemonstrated to affect symptom perception and illness behavior. Future studiesare also likely to identify psychological and behavioral interventions that aretargeted for this subgroup.While it is likely that there are potent new treatments that will follow our growingpathphysiologic knowledge of these disorders, it is unlikely that they will replace some of thefundamental clinical principles active listening,o careful decision making,o an effective patient-physician relationship, ando patient centered biopsychosocial plan of care.http://www.med.unc.edu/wrkunits/2depts/med...aldisorders.pdfYou seem to be looking at this with the dualism theory. That creates problems with understanding it and the most effective ways to treat IBS and ALL the triggers to it. It can also perpetuate somewhat the notion its made up or the brain has nothing to do with it as well as makes things harder to explain the intereactions of the brain gut axis to IBSers themselves and education on the disorder and hence they may miss out on very benefical treatment approaches or even harmful ones sometimes.


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## SpAsMaN* (May 11, 2002)

http://www.ncbi.nlm.nih.gov/sites/entrez?c...pt=AbstractPlus


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## eric (Jul 8, 1999)

That study was done in 2002 on 10 people via autopsy. They had passed away and that gave the researchers a chance for dissection.Dr Spiller wrote a good commentary on this, but I need to find it.But once again I need to remind you inflammation cannot be a biological marker for IBS.This is also a lot newer from DR Wood, who I am sure you are aware of as a top IBS research doctor.ISSN 1007-9327 CN 14-1219/R World J Gastroenterol 2007 March 7;13(9): 1313-1332Neuropathophysiology of functional gastrointestinal disordersJackie D Woodhttp://216.109.125.130/search/cache?ei=UTF...=1&.intl=us


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## 14633 (Jan 5, 2007)

HiI have tried reading this email trail and must admit that its a bit overwhelming. However, I gathered bits and pieces of the information provided.I have got IBS-C for nearly 5 years now. I have found a close direct relationship of the severity of my IBS and histamine levels in my body. During the spring season when there are lots of pollen in the air my IBS was worse and I had an abdominal cramping.RegardsRSB


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## eric (Jul 8, 1999)

RSB, Histimine can be released for a lot of different reasons. It seems to play a role.also Gastroenterology. 2007 Oct;133(4):1113-23. Epub 2007 Jul 25. LinksAltered rectal perception in irritable bowel syndrome is associated with symptom severity.Posserud I, Syrous A, Lindström L, Tack J, Abrahamsson H, Simrén M.Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.Background & Aims: Diverging results exist regarding the connection between altered visceral perception and gastrointestinal (GI) symptoms, as well as the effects of psychological status on visceral sensitivity. We sought to investigate different aspects of rectal perception in irritable bowel syndrome (IBS) and the association with GI and psychological symptoms. Methods: We included 109 patients with IBS meeting Rome II criteria (77 women; age range, 20-71 years) and 29 healthy controls (21 women; age range, 20-68 years). They underwent rectal balloon distentions determining sensory thresholds for discomfort and pain, the perceived intensity of unpleasantness, and the viscerosomatic referral area. The fifth percentile (thresholds) and 95th percentile (unpleasantness and referral area) in controls were used to define altered perception. Questionnaires were used to assess severity of IBS-related GI symptoms and psychological symptoms. Results: When combining the 3 aspects of perception, 67 patients (61%) had altered rectal perception. These patients, compared with normosensitive patients, more frequently reported moderate or severe pain (73% vs 44%; P < .01), bloating (73% vs 36%; P < .0001), diarrhea (47% vs 21%; P < .01), satiety (39% vs 13%; P < .01), and clinically significant anxiety (31% vs 12%; P < .05). In a multivariate analysis, only pain and bloating remained associated with altered rectal perception. Conclusions: Altered rectal perception is common in IBS and seems to be one important pathophysiologic factor associated with GI symptom severity in general and pain and bloating in particular. It is not just a reflection of the psychological state of the patient.PMID: 17919487


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