# Instead of talking about symptoms and treatments...



## 19277 (Mar 26, 2007)

I would like to open discussion as to the cause of IBS and other digestive disorders. Further, I would like to debate on my position that conventional medicine is fundamentally flawed when it comes to viewing diseases and disorders which implicates why they have huge failure rates when it comes to successfully treating and healing disorders such as IBS.I know it sounds heavy but there are some bright minds out there who can run with me on this.I have been kicked off of 2 other IBS forums for trying to start this diatribe, so if you want to, maybe you should email me.


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## 16229 (Jan 28, 2006)

I'll comment, but please, no scare tactics. It's perfectly acceptable to talk about these things, but it's not okay to scare people into thinking they have problems that they don't.


> quote:I have been kicked off of 2 other IBS forums for trying to start this diatribe


Well, at least we are starting off honestly.


> quote:which implicates why they have huge failure rates when it comes to successfully treating and healing disorders such as IBS


 I wouldn't call 5% a huge failure rate. 95% with IBS are treated successfully without the use of too many drugs.Look, I'm not the hugest fan of the medical system, but it's not fundamentally flawed outside of the insurance/payment system which prohibits quality care. I also find some fault in the way the FDA and meds are set up, but that's hardly systemic. For that, there just really needs to be a President that isn't scared of big business and will set a couple of things right.If you aren't going to use symptoms to dx things, how do you? Doc, I don't feel well. What's wrong? If you didn't give symptoms you wouldn't even be able to start.GI issues are difficult because there are many possible factors and they often present alongside another problem. They don't receive as much research money as cancer, AIDS and others. And I don't see too much wrong with that seeing the fatality rate of IBS vs. cancer. Still, knowledge of these problems has come a long way in the last 20 years. We are in the infancy of truly understanding the complex relationships both in the gut and between the gut and other body parts and systems.It is also challenging because what we know as IBS is probably multiple related disorders. I think we are already seeing Post infectious IBS be seperated from the pack a little bit and you will see more of that in the coming years. Informally, there are already IBS-C,D,A, though from what I've been told the disorder probably does not cut straight down those lines.IBS works off of several main body systems. What we eat or drink, prescence or lack of a multitude of bacteria and microscopic organisms, the enteric nervous system and possibly some components that play a little off the central nervous system, the connections to the mind, etc. You have literally millions of things or combinations of things that could go awry and cause problems in the gut. When you consider that different people probably have slight differences in these relationships, the probability of finding an answer for everyone over any short duration of time is literally billions to one.To me, that would indicate modern medicine has done a pretty good job over the last 30 years. If 95% of these people are considered treatable with at most, small amounts of prescripton drugs. 80% without the use of medication at all.What you are seeing in research are small steps being taken to identify aspects to IBS, evolve a more and more consistent methodogy for diagnosis, and learning about the foundation of the gut's relationship with other systems in the body in IBS. What does knowing about visceral hypersensitivity do for me, the IBS sufferer, today? Not much. But for researchers, it's one piece of the foundation. It gives us a common manifestation in most with IBS and it also gives us a look into how the gut works, in this case, with the nervous system and the mind.But, how much do we even know about these parts of the puzzle? We don't even really know how nerves communicate with each other. So if we have a problem where nerve centers relay information incorrectly from the gut to the mind, you are creating a multi dimensional relationship that, unfortunately, science does not understand yet. The only way to treat it is to get a little lucky, but even then the chances of any single thing working are minimal.As to the cause I think science is trying to get to how the body runs on every basis, even chemical. But science is a long ways off from understanding all these things.Look, I'm happy you've found your answer. Just like I'm happy for everyone who does, many on here who have found things that worked outside of their doctors offices. But as you said, our bodies are different and what works for one may not work for another.In the last decade I've been both in and outside of the box. Being outside of the box has done me no more good than being in it. I've seen good drs, bad drs and quite a few exceptional ones. I've had normal md's go "outside the box" in my treatment. I've been on more meds, diets, supplements, probiotics, therapy, meditation and on and on.To make a blanket statement that the entire medical community is tied to a pole is just way off. It is true that most large institutions follow a linear pattern, but there are hundreds of other facilities out there doing research that fit all over the paridigm.


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## eric (Jul 8, 1999)

Good post artjunky.







Steve, do you personally understand this?"*Enteric Nervous System*Posted 03/03/2006David Grundy; Michael SchemannAuthor InformationAbstract and IntroductionAbstractPurpose of Review: Our aim was to provide a synopsis of how the field of enteric neurobiology has advanced during the past year.Recent Findings: With such a large number of studies to choose from and given our emphasis in last year's issue on developmental aspects of the enteric nervous system, we have focused on several key themes reflecting the current interest in the way the enteric nervous system is altered in disease.Summary: The new basic science information gathered during the past year provides insight into pathophysiological processes and will pave the way for improved understanding of both organic and 'functional' gastrointestinal disorders.IntroductionThe enteric nervous system (ENS) is considered to be an independent nervous system that controls and coordinates motility, blood flow and secretion to meet the digestion needs of the individual. It contains an estimated 108 neurons in two major ganglionated plexuses that extend the entire length of the bowel in two major layers: the myenteric plexus between the longitudinal and circular muscles and the submucosal plexuses associated with the mucosal epithelium. Reflex function independent of the central nervous system (CNS) arises because of the coordinated activity in sensory neurons, interneurons, and excitatory and inhibitory motorneurons. The ENS is connected to the CNS, however, by both afferent and efferent pathways. The former are the basis for sensation of gut origin, particularly pain but also non-painful sensations such as fullness, bloating, and nausea while efferent connections provide the parasympathetic and sympathetic innervation that helps control and coordinate the different regions of the gastrointestinal tract with their different regional specialized functions.The neural mechanisms that coordinate gut function rely on a complex interplay between many neuroactive mediators and their receptors. Progress in the past year has helped our understanding of the neuropharmacology of enteric transmitters, ion channels and receptors responsible for the modulation of neuronal activity and the organization of neurally mediated reflex responses. Studies of the enteric innervation are complicated by both qualitative and quantitative differences in neuronal phenotype that exist between species and which often make it difficult to extrapolate to humans. That is why below we focus attention where possible on recent advances gained from studying human tissues and cells. In this way there have been significant advances that have helped to shed light on the pathogenesis of gut disorders (both organic and functional) and at the same time provided opportunities for novel treatments. Here we describe some of these advances with a focus on changes in reflex function that occur under pathophysiological circumstances, in particular in inflammation, postoperative injury, ageing and irritable bowel syndrome. These studies highlight the link between the ENS and the immune system and may lead to treatments aimed at modulating neuro-immune interaction.5-HydroxytryptamineThe use of serotonergic agents in patients with irritable bowel syndrome (IBS) is based on the critical role that 5-hydroxytryptamine (5-HT) plays in the maintenance of normal gut function and brain-gut communication.[1*] 5-HT3 and 5-HT4 receptors have proven to be valuable targets for the treatment of diarrhoea-predominant and constipation-predominant IBS respectively, while 5-HT7 receptor subtypes may also be promising targets for the future. Some contradictory observations, however, have still not been adequately explained and detailed receptor pharmacology requires further evaluation.[2*] A recent study[3] provided evidence for the heteromeric assembly of excitatory 5-HT3A/B receptors in human enteric neurons. While submucosal neurons express the receptor, however, it is surprising that their pharmacological activation does not evoke a secretory response in human intestine as in other species. 5-HT4 receptor agonists have been available for some time for the treatment of constipation predominant IBS, but the mode of action is not completely understood. Liu et al.[4] studied the localization and function of 5-HT4 receptors in the mouse ENS. 5-HT4 expression was found in the neuropil of submucous and myenteric ganglia as well as in nerve fibres of the circular muscle but not in the mucosa. Although transcripts encoding 5-HT4a and 5-HT4b isoforms were abundant, interestingly those encoding 5-HT4e and 5-HT4f were myenteric plexus-specific. 5-HT4 receptors presynaptically enhanced fast synaptic transmission and this increase in acetylcholine release may contribute to the prokinetic effects of 5-HT4 agonists. In contrast 5-HT7 receptors may modulate the nitric oxide-mediated accommodation process.[5*] Activation of the 5-HT7 receptor resulted in intestinal relaxation and the authors have proposed that the 5-HT7 receptor may be a novel target to treat diarrhoea-predominant IBS. Interestingly, the 5-HT7 receptor mediates its effects through activation of nitric oxide synthase (NOS) neurons in a similar way to that described previously for 5-HT1p mediated responses.[6] In addition 5-HT7 receptor blockade reduced the slow excitatory synaptic transmission in enteric AH-neurons,[7**] a response that has also been attributed to the 5-HT1P receptor. The enigmatic 5-HT1p receptor has not been correlated with any known 5-HT receptor gene product and a preliminary report suggested that dimers of the 5-HT1B/1D receptors and the dopamine D2 receptor may account for some properties of the 5-HT1P receptor.[8] Despite this uncertainty of the 5-HT1p, the question arises as to whether 5-HT1p and 5-HT7 receptors share some common functional and pharmacological properties. Functional 5-HT7 receptors are present in human microglial MC3 cells, suggesting that they are involved in neuroinflammatory processes.[9] It is intriguing to speculate that the 5-HT7 receptor may be one of the missing links between the changes in serotonin signalling and metabolism and the symptoms experienced by post-infectious IBS patients."http://www.medscape.com/viewarticle/524224_2I can say with some certainty there are not to many naturopaths who actually DO this kind of research.Proably not to many who understand it for the most part either. I know I don't understand it fully for sure, but there is such a thing as evidence based medicine. Not that naturopaths can't help some people with somethings.


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## 19277 (Mar 26, 2007)

Ok, thanks for the the replies. Here are two responses at once.First Ericespite huge advances in subjects like genetics, molecular biology and even in things like research to the "enteric nervous system" the sad fact is that the practice of medicine has changed very little in the last 40 years.For example, even with all the new and cool research from various fields, clinicians have a hard time integrating into their practices. I believe that the reason for this is that clinicians, medical researchers and the like simply look too much to symptoms to help explain a disease rather than trying to identify theunderlying cause of the disease. Which they are failures at doing because their scopes are myopic. Further, MD's as a result lack the ability to heal people.Thanks for all the amazing info Eric, but I am no longer impressed by your lengthy cut and pastes. Let's see a real analytical thought out of you instead of you hiding behind long abstracts that even you don't understand.To the next one:


> quote:Look, I'm happy you've found your answer. Just like I'm happy for everyone who does, many on here who have found things that worked outside of their doctors offices. But as you said, our bodies are different and what works for one may not work for another.


I found something that worked INSIDE a doctors office. This doctor was way more impressive than any MD I have seen, and I have even been exposed to the Mayo Clinic. This incredible doctor just happens to be a ND.And it is true, our bodies work different...how this guy operates is that he uses an area of science for clinical evaluation that has been developed over the last 20 by a number of Ph.D's from Berkley and other impressive schools. This area of science has the ability to analyze all patients with varying disorders as individuals. It tells them how they are functioning (or malfunctioning) uniquely, and then it builds an appropriate treatment plan.While I support evidence based medicine, conventional medicine is hardly evidence based. They can do some tests and analysis but the majority of treatments are prescribed based on clinical evaluation of symptoms. Which, in my opinion, is one of the fundamental flaws of conventional medicine because the cause of may symptoms may be different enough from the cause of your symptoms...then the treatments don't work similarly.Imagine you could walk into your dr.s office, have him analyze you objectively (outside of his/her opinion) and then tell you "this is what's wrong with you and this is why". When he explains what's wrong with you, he mentions no disease labels and tells you why you experience this conglomeration of symptoms that other MD's label as a disease. He then tells you how he can fix the underlying cause and, somewhat magically, your disease disappears.That is what I experienced. Further, there is much objective scientific information that backs it. There are over 6,000,000 publications on pubmed. NO doctor anywhere could reasonably be expected to keep up with this. Hence another flaw with our system, i.e. no one can integrate all of the information to a unified and grand theory of medicine because the information base is to large and most of the information comes from very different perspectives. What I experienced was a theory that explains the basic and unique function of the human body...and as a result has the ability to explain the body's dysfunction thus identifying the cause of disease and treating it.


> I wouldn't call 5% a huge failure rate. 95% with IBS are treated successfully without the use of too many drugs.
> 
> 
> > Artjunky, please show me where you get these figures and I will explain to you why they are completely false or misinterpreted.Thanks for the stimulation all,


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## 23240 (Mar 25, 2007)

I'm tending to agree with Steve in this debate. My own limited personal experience with a GI and a GP in a college town is that when they can't explain something they fall back on an IBS diagnosis. It's as if IBS is everything that can't be explained or treated successfully by them.I also think it's important to evaluate the economy of conventional medicine. There is a growing market in medicines that can promise treatment and even cures for IBS (just spend some time looking around this board). It's extremely depressing, frankly, to see so many desperate people turning to doctors who have such a limited understanding of the human body. I was shocked to read one poster writing about suffering with IBS for years only to recently discover yogurt and probiotics. I would think that would be the first thing a doctor suggested.


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## 17890 (Mar 11, 2007)

I would just like to say that I think questforhealing shares really good points. I have been totally unimpressed with MD's who have seen me here in Spokane. One doctor spent five minutes with me, asked me what I feel like (I have normal bowel movements, diarrhea very rarely and horrible bloating), he said I have IBS based on symptoms. I am a college student and have spent so much money trying to get answers. I now see an awesome naturopathic who talks to me, addresses all concerns and wants to get to the bottom of this. I may have a mild form of IBS but she honestly thinks there may be something else going on, and she is "thinking outside the box" in order to help me. I have had WAY more success with a ND because of the way they approach health issues.-Miranda


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## eric (Jul 8, 1999)

Gardiner Harris You might ask this question on the 5ht 4 forum.There are different conversations going on here, bad doctors and IBS research. Two different issues.questforhealing, so the ACTUAL research on how the enteric nervous system and central nervous system (brain and spinal cord) physically works does not impress you or does it seem to matter to you.Again ND don't have the qualifications or medical expertise for this kind of research and if a few do they would be doing this kind of research and would have to have other researchers confirm theeir findings, thats how it works in science. Where do ND's get their information FROM? Some that have posted here in the past have flat out posted bad information, like IBD and IBS are the same. Its also known there are some thirty functional disorders and those classifications are important to the problem or problems people experience."You should keep in mind that all scientists will from time to time try to extend their data into understanding other aspects of a condition, but the checks and balances within medicine lead to common acceptance when there is confirmation from other groups and more conclusive evidence."Dr DrossmanDr Spiller is one if not the leading expert in Post infectious IBS. Post infectious IBS is a type of model, as well as animal studies for IBS research, along with IBS patients in general.Post-Infective IBSPost-infective IBS is the name given to the condition suffered by a number of patients with Irritable Bowel Syndrome who report that they had normal bowel habits prior to a bout of gastroenteritis, diarrhea and/or vomiting. Post-infective IBS without concurrent anxiety, depression or neurotic presentations has a relatively good prognosis and recovery is more rapid.The most common causes of the gastroenteritis are viral, followed by Campylobacter, Salmonella and Shigella. Viral gastroenteritis typically heals rapidly with little residual damage to the gastrointestinal wall. However, bacterial gastroenteritis on the other hand can often produce ulceration and bleeding, and is more likely to be associated with with post-infective IBS. Spiller studied 386 cases of bacterial gastroenteritis obtained from a community survey. The average duration of illness was seven days with a third of patients reporting bloody diarrhea and a median weight loss of 6kg.Travelerâ€™s diarrhea is extremely common in Australians travelling to Asia and Indonesia, as it is in Canadian citizens traveling to Mexico. In one study of Canadian travelers nearly 50% developed travelers diarrhea and the incidence of new IBS three months later was 17.5% compared with just 2.7% for those who did not get travelers diarrhea. Post Infective IBS risk factorsDiarrhea and vomiting is a normal reaction to infection and helps to clear the gastrointestinal tract of infection. Most patients with bacterial gastroenteritis recover fully and only about 10% seem to develop post-infective IBS. The risk factors are:Being of the female sex, Hypochondriasis (although it could be argued that the "hypochondriasis" is the result of some predisposing weakness) Adverse life events in the previous year Duration of the initial illness is a very strong risk factor for post-infective IBS The specific infecting bacteria is likely to be important, since Spiller found around 10% of Campylobacter infected individuals developed post-infective IBS, compared to just 1% with Salmonella. The severity of tissue damage and ulceration may be major predictor. post-infective IBS PATHOPHYSIOLOGY Diarrhea related illnesses are characterized by faster Gastrointestinal transit time and increased gut sensitivity. This gradually returns to normal, but may do so at a variable rate. By three months, most of those who are going to recover will have done so and thereafter the rate of recovery is much slower. Spiller and colleagues performed longitudinal rectal biopsies in individuals recovering from Campylobacter gastroenteritis at 2, 6, 12 and 52 weeks, and noted initial increases in both inflammatory cells and enteroendocrine cells. Most returned towards normal, but in a few markedly symptomatic individuals the biopsies remained abnormal. Similar abnormalities were noted in patients attending the outpatients with a history of post-infectious IBS. There is a good correlation between the inflammatory cells and the enteroendocrine cells, which Spiller interpreted as suggesting that cytokines might drive the enteroendocrine cell hyperplasia.Other authors have noted increased enteroendocrine cells in unselected IBS patients but this needs confirmation. More important than increase in numbers may be the increase in release of 5HT. Several pilot studies have suggested that there was an exaggerated release of 5HT following a meal, particularly in those who got meal-related symptoms. Treatment of post-infective IBSIt is important that patients understand the important roles of anxiety, stress and diet and persisting low-grade inflammation in this condition. Providing the Rome criteria are met and general physical examination is normal, then the probability of an alternative diagnosis is low. However, infections can unmask other disease, particularly celiac disease, inflammatory bowel disease such as Crohn's, and tropical sprue together with hypolactasia. Such patients should, therefore, undergo a minimum set of screening tests, including endomysial antibodies, hemoglobin, CRP, ESR, albumin and stool culture. In the absence of alarm features such as weight loss, fever, rectal bleeding and nocturnal diarrhea, only 5% of all these tests are likely to be abnormal. Since microscopic colitis has also been reported to develop acutely after an infectious illness, it is important to do a colonic biopsy and, if suspicions are high, also a duodenal biopsy to exclude celiac disease.Lactose intolerance developing after a viral gastroenteritis is well recognized by pediatricians. This occurs because lactase, the enzyme responsible for digesting lactose, is expressed fully only in the mature enterocyte at the tip of the villus. Since viral gastroenteritis generally specifically damages the villi, lactase levels remain low for some months. A low lactose diet is, therefore, worth trying.Since psychological factors are so important, it is necessary to make some formal assessment of the causes of the anxiety and depression. Where anxiety and depression levels are high, they should be treated on their own merits, since it is unlikely the patient will recover without addressing these psychological issues concurrently.Its pretty well known that some perhaps 30% or more even people develop clinical IBS from PI IBS.questforhealing, you have not posted any science or any studies on any causes, or any research already done on IBS, all you have posted are your opinions.


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## Jannybitt (Oct 13, 2006)

Artjunky;I am so impressed at how you put this in a "language" per say, that the average reader on here can interpret. Thank you!! It was an understandable piece and your reasonings were right on!! You will never be able to put "it" all in one box.I think maybe the "flaw" here runs a couple of ways. One, there are doctors who are intimidated by a disorder that does not have one treatment for everyone.I think the 2nd "flaw" is with the patient who does a couple of things: visits their doctors with vague symptoms, are not prepared when they go in, and take the first answer their doctor gives them, or worse, stops seeking help after they hear "it's all in their head". Becoming your own advocate is a huge key to me in helping researchers help us. If that makes sense?I do think IBS is a very complex "functional" disorder that is mind-gut oriented, and when you are dealing with those two factors, you are now involving not only the medical field, but also the psychological field, and in alot of instances, these two fields do not mesh well.Do I think there will ever be a straight cure that will come through medical research? No. I think they will eventually find a combination of treatments, and I don't think we'll see it as just a drug treating cure. I think, overall, in the 9 years that I have had IBS, there has been forward measures that have been taken - I hear about studies all the time, my different doctors over the years are finally hearing things, taking notes, taking an interest! But, so much of that is in the responsibility of the patient and conveying themselves to their doctor. I have seen drug treatments available that I hadn't 9 years ago, I've seen many more natural treatments that have shown success in many patients. I am one of those patients that rely on the treatment of medications and natural treatment. I am grateful for a doctor that will do trial and error with me on those medications. I am grateful for these meds, because I can live my life with quality. I think we will see baby steps throughout this process of researching IBS, but who knows? We might be surprised.I'm sorry, I'm not sure if this fit into the debate you were looking for Steve. I don't see huge failure rates in this area. Maybe because I am living life, for the most part, with quality. And, because I'm not dying from a terminal illness.


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## eric (Jul 8, 1999)

FYIDiagnosing IBShttp://ibsgroup.org/groupee/forums/a/tpc/f...261/m/316101372Chronic Abdominal Pain in Children Subcommittee on Chronic Abdominal Pain "The pathophysiology of functional abdominal pain is thought to involve abnormalities in the enteric nervous system (ENS), a rich and complex nervous system that envelops the entire gastrointestinal tract. The ENS is also known as the "gut brain" or the "little brain in the gut."2 The ENS interacts with the central nervous system, allowing bidirectional communication. A dysregulation of this brain-gut communication plays an important role in the pathogenesis of functional abdominal pain. Most of the research on childhood visceral pain in the 1980s and early 1990s focused on the role of motility disorders and psychiatric abnormalities. Recently, however, more sophisticated diagnostic techniques have failed to identify motor abnormalities severe enough to account for these patients' symptoms. It is now believed that adults and children with functional bowel disorders, rather than having a baseline motility disturbance, may have an abnormal bowel reactivity to physiologic stimuli (meal, gut distension, hormonal changes), noxious stressful stimuli (inflammatory processes), or psychological stressful stimuli (parental separation, anxiety).3 Additionally, adult patients with functional bowel disorders attending gastrointestinal clinics were often found to have psychological disturbances regardless of the final diagnosis. It was concluded that psychological factors may have been more important in determining health-seeking behavior than the cause of the symptom.4 There is growing evidence to suggest that functional abdominal pain disorders may be associated with visceral hyperalgesia, a decreased threshold for pain in response to changes in intraluminal pressure.5,6 Mucosal inflammatory processes attributable to infections, allergies, or primary inflammatory diseases may cause sensitization of afferent nerves and have been associated with the onset of visceral hyperalgesia.7 The concept of visceral hyperalgesia may be explained to the patients and family members comparing gut hyperalgesia to what happens when one experiences a burn or a scar: the skin may remain sensitive for prolonged periods of time and perceive as noxious even stimuli that are normally not uncomfortable (such as contact with clothes). There is also an increasing body of evidence in adults suggesting that an abnormal central processing of afferent signals at the level of the central nervous system may play a role in the pathophysiology of this condition.8,9 Functional abdominal pain is the subject of many misconceptions in both the health care and lay communities. http://pediatrics.aappublications.org/cgi/.../full/115/3/812with permission from the UNC"*History of Functional Disorders*Douglas A. Drossman, MDCenter-Co-DirectorMelissa SwantkowskiNew 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 to understand and categorize them. Systematic investigation of functional GI disorders did not begin until the middle of the 20th century, and prior to this time, only occasional reports of functional GI symptoms were published, the first appearing only 200 years agver the past 25 years, scientific attention to understanding and properly caring for patients with functional GI disorders has grown progressively. With the understanding comes the rationale for use 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 of scientific publications and greater media exposure to the public through television, radio, and Internet.To understand the historical classification of these disorders, two differing theories relating to the interaction 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, the study of medical disease must take into account the whole person rather than merely the diseased part. However, societal concepts of illness and disease drastically shifted when European philosopher Rene Descartes offered the divergent theory of dualism in the 17th century. Prior to the notion of dualism, the church discouraged human dissection on the premise that the spirit resided in the body. The acceptance of dualism paved the2way for the emergence of scientific investigation and new medical discoveries by lifting the prohibition of human dissection. This shift in medical thought was congruent with the societal changes of the 17th century: the shift towards a separation in church and state.IMPLICATIONS FOR FUNCTIONAL GI DISORDERSBased on the concept of dualism, disease was now understood in terms of structuralabnormalities. Therefore, the validity of a disease rested with the observation of morphological abnormalities. Medical conditions occurring in the absence of such morphological abnormalities and 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 considered amenable to scientific inquiry and treatment. However, patients with psychiatric disorders were interred 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 their symptom presentation and clinical behavior. Gastroenterologists (as well as other health care practitioners) are all too familiar with the poor correlation between structural findings on endoscopy and their patient's symptoms.Although efforts to find morphological or even motility etiologies for functional GI disorders in the latter part of the 20th century were unsuccessful, the assumption that functional GI disorders must be psychiatric has developed and has permeated current thinking. However, in the face of current scientific research, this is being seriously challenged. Studies have shown that persons with irritable bowel syndrome who do not seek health care are psychologically much like healthy subjects.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 to3 understand, categorize, and treat common GI symptoms. These symptoms are the integratedproduct of altered motility, enhanced visceral sensitivity, and brain-gut dysregulation and often are influenced by psychosocial factors. Figure 1 illustrates the proposed relationship between psychosocial and physiological factors with functional GI symptoms and the clinical outcome.Early in life, genetics and environmental influences (family attitudes toward bowel training or illness in general, major loss or abuse history or exposure to infection) may affect one's psychosocial development (susceptibility to life stress, psychological state, coping skills, social support) 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 interaction of psychosocial factors and altered physiology via the brain-gut axis. In other words, one individual afflicted with a bowel disorder but with no psychosocial disturbances, good coping skills 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 methods that 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 psychosocial influences,4. the introduction of brain imaging (PET, fMRI) to determine CNS contribution tosymptoms, and 5. the molecular investigation of brain-gut peptides, which provide insight into how these 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 symptoms that 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 a larger effort to address issues within gastroenterology that are not easily resolved by usual4 scientific 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) in 2000 as well as the publication of a supplement to the journal Gut in 1999. Recently the Rome Coordinating Committee has met to begin Rome III, expected to be published in 2006. To learn more 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 large intestine and colon. Abnormal motility can generate a variety of GI symptoms includingvomiting, 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 normalintestinal 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.5BRAIN-GUT AXISThe concept of brain-gut interactions brings together observations relating to motility andvisceral 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 enteroceptiveinformation (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 stresshormones 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, 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 FACTORSAlthough 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 referral centers than in primary care and is associated with a more severe disorder and a poorer clinical outcome. Additionally, psychological trauma may increase painreporting tendency.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 physician patient relationship. The basis for implementing a strong physician-patient relationship is supported by evidence that patients with functional GI disorders have anywhere from a 30 to 80% placebo response rate regardless of treatment.6Because 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 patientï¿½s illness behavior, and the degree of functional 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 their physician. Regarding treatment, these patients require education about their disorder and its symptoms as well as information regarding a proper diet and the kinds of medication that can have 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 associated factors can help to identify inciting factors and give the patient a sense of control over the disorder. Additionally, pharmacotherapy directed at specific symptoms, particularly those that impair 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 for these patients needs to shift from treating a disease to coping with a chronic disorder, where much of the responsibility is place on the patient, himself. Furthermore, antidepressants have proven useful to control pain and alleviate associated depressive symptoms.7THE FUTUREFuture studies will identify pathophysiological subgroups, each having its own set ofdeterminants and treatment. Examples are as follows Some patients will develop their disorders or exacerbate symptoms via sensitization of afferent transmission from infection, enhanced motility, or trauma to the gut. They may respond to the newly developing eurotransmitter blocking agents.o Patients with more painful and severe symptoms may prove to have "abnormalperception of normal gut function" rather than abnormal function. This dysfunction in the central regulation of incoming visceral signs may be remedied with 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 are targeted 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 the fundamental 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/medicine/fgidc/hist...aldisorders.pdf


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## 19277 (Mar 26, 2007)

I just typed a lengthy reply to you eric...but I closed it out before publishing.In short, trying to justify your position with science that you do not understand presents a very weak standpoint.Your insinuation that I do not understand how science works is not appreciated. I would be happy to discuss the philosophy of science with you in detail. keep in mind that I have an advanced degree in statistics which is the _heart and soul of the scientific method_ I am not impressed by any research you have tried to present because ALL OF IT fails to identify true cause of disease or functioning of the human body or interaction of all bodily processes.I found an ND who is more brilliant than any MD I have experienced and he is the first person to have the ability to implement human biochemistry as a mode of analysis and treatment very well. In short, he told me what all of the underlying causes of my symptoms were. And the interesting thing about this is that all MD's told me that my abundant symptoms in all parts of my body were unrelated.Dr. Neustadt, upon analysis, told me how my seemingly disparate symptoms were interrelated and HOW.You see, his philosophy is amazingly more powerful than the one MD's are operating under. There will be much scientific evidence and replication in the years to come.Upon treatment by him, which was a very specific and targeted natural treatment, my IBS, GERD, Sjogren's, symptoms as well as joint aches, muscle aches, inability to eat large amounts of food, sinus symptoms, etc literally disappeard in a matter of weeks. And this happened after year of constant symptoms.He told my I had these diseases and disorders. He told me how they were related. He told me how to correct the fundamental dysfunction of my body. He cured me period. And every day that goes by I get better...He is going to save many lives that are in danger from chronic degenerative diseases.I am so glad to hear Zelnorm is removed. I took it for a year and it gave me very weird and sometimes alarming side effects.the FDA and the pharma's have a poor track record. People are dying under their treatments. Why is it ok for us to accept the risk that a certain percentage of people will die under a given drug treatment.there are ways for us to become well without this risk...If any one is interested in my story, it is on my home website.


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## eric (Jul 8, 1999)

Hey I am glad he helped you.You wanted to have this discussion.Does he have any articles in peer reviewed journals? Does he do his own real research or just study others research?Was he the one that identified that there are some 500 gut bacteria?Is he the one that discovered and identified the enteric nervous system and that is has as many nerve fibers as the spinal cord and all of the chemicals found in the brain?Does he have the expertise to do pet and fmri imaging and interpret the results?Does he look at celluar structure of the digestive system under an electron microsope?"Imagine you could walk into your dr.s office, have him analyze you objectively (outside of his/her opinion) and then tell you "this is what's wrong with you and this is why". When he explains what's wrong with you, he mentions no disease labels and tells you why you experience this conglomeration of symptoms that other MD's label as a disease. He then tells you how he can fix the underlying cause and, somewhat magically, your disease disappears."Did he do any testing or just cure you with words?So he understands and can cure everyone on the planet of every condition and completely understands all the complexities of how the brain works, gut works and everything about how the body works? I hope you really understand how that really sounds."he told me what all of the underlying causes of my symptoms were"So what was the problem he told you you have?


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## eric (Jul 8, 1999)

FYIMore women then men have IBSLadies home journalThe Gut-Brain Connection Recent studies show that functional GI symptoms are not necessarily the result of dysfunction in the bowel, but may be due to disturbances in brain-gut pathways. By Harvard Health Reports http://www.lhj.com/lhj/story.jhtml?storyid...on_08122002.xmlaltered gas dynamics in IBSReport from IFFGD Research Award WinnerUnderstanding Intestinal GasBy: Fernando Azpiroz, M.D., Ph.D., Chief Section GI Research, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.Dr. Azpiroz is the recipient of the IFFGD 2005 Research Award to Senior Investigator, Clinical Science. Dr. Azpiroz's clinical practice develops in a large referral unit, and specifically focuses on functional gut disorders. His research program investigates the origin of gastrointestinal symptoms and involves both physiologic and pathophysiologic aspects of the control mechanisms of gut motility, visceral sensitivity, and more recently, intestinal gas dynamics (the movement of gas through the gut).http://www.giresearch.org/Azpiroz.html


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## administrator (Aug 20, 2004)

Since this topic is likely to lead to an endless debate and is not directly about IBS, it is being moved to the IBS News, Research and Abstracts forum.


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## Jannybitt (Oct 13, 2006)

I am going to share this point to you, Steve and a little to you also, Eric.Steve, you requested a debate or conversation, if I'm not correct? I always feel if someone opens up a discussion for others to put in their opinions and share, those should be at least acknowledged. I don't know you, Steve, but you sound very intelligent. I know you some, Eric, and know that you are very intelligent also. But, do you both realize that the other people (one being me) that attempted an opinion with people that are intelligent enough for it to be intimidating, that you both rolled over the top of a few of us like we never interjected anything whatsoever. Not only is it rude, it is demoralizing. Apparently, I was way out of my league attempting to interject into this debate, conversation, argument, whatever you would like to call it. Steve, the next time you would like to start a debate, maybe give that a little thought. You too, Eric. At least you gave Artjunky some kudos for his posting. It makes me wonder why you got kicked off two other sites, Steve. When there is a forum that invites all walks of life to join, there should be universal respect. I've learned my lesson for the next time not to go past my comfort zone because I thought I had something worthwhile to post.


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## eric (Jul 8, 1999)

Jan, my humble appologies to you and I didn't mean to ignore your post in the slightest. I actually agreed with it and thought you put things in perscpective as well with reason. I should have posted and acknowledged it however. I got caught up in the moment and my thoughts on this thread.You know I should have never taken the bait, I really should have let this go, but it concerns me that threads like this, create more worrying about every possible cause of IBS and and less trust in people's doctors and the diagnoses of IBS. Like every MD or IBS researcher are all enimies. This is not true of course and they are greatly helping us ALL out, each with their own research and with combined research.


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## 16229 (Jan 28, 2006)

First off, thanks Janny. I am a real person so I try to convey things in a manner people can understand. I know it took me a long time to figure some things out because I didn't understand the language it was spoken to me in. I think we have a lot of information on this board, but it doesn't help much if you don't comprehend what you are reading.I agree with a lot of things said about the normal doctor's practice. That is the reason we all need to find the right one, whether they be a MD, DO or ND. You need to find doctors you trust, can talk to, who will be straight with you and listen to your ideas when it comes to treating you and your body.But still, most problems come from the way the payment and insurance systems are set up. When you see the doc, the insurance company gets the bulk of the money, a trend which has gotten worse year after year. So every year a doctor has to fit in a few more patients to make the same money they made the year before. The result is the doctor not being able to spend enough time with each patient, may be restrictive to certain therapies or testing etc.I will also agree docs put too much into IBS. If it can't be classified anywhere else, then it gets lumped onto IBS. It's a double edged sword. For some, it can make understanding what is going on tougher and can confuse things. But you must also look at the flip side of the coin. Gastro issues are served with a healthy size of anxiety in many cases. If I have anxiety and the doc says he has no clue what's going on my anxiety, and by extension my gastro problem, will most likely get worse.It can be hard, even for the docs, to keep up with all the new stuff coming out. It's important for us to find GI's that are up to date and hopefully attend some of the larger seminars annually where large groups of GI's get together and learn about new treatements, info, etc. Sometimes going to a practice with multiple GI's can be a good thing, as they are more able to attend these learning seminars than a GI in a single doctor practice may.I think insinuating doctors as a whole do not care and do not want to get to the bottom of things is complete ####. I am a very unique case. I've seen at least 100 doctors over the last decade, including specialists from all over the spectrum. I've never thought a single one didn't want to help me.


> quote:Artjunky, please show me where you get these figures and I will explain to you why they are completely false or misinterpreted.


 I don't keep a huge log of info on hand. These numbers are pretty well known and I have seen them cited quite a few times. It was from a survey of those who had IBS, so I would think that is compelling.Steve, I'm a little confused as you seem to contradict yourself quite a bit. You continually talk about how the medical community is stuck in a restrictive mold, but then say there is too much info out there from too many different perspectives. I thought differing perspectives was a good thing?You say he told you what diseases and disorders you had. But you also said he views you objectively without labeling you as having a disease or disorder. I'm just a little confused by that.Modern medicine and science understand the underlying factors of many diseases and disorders. Just because IBS isn't completely understood doesn't mean others aren't. Auto-immune disorders are also misunderstood, but that is in part due to the extremely complex relationships in the body that they are a part of.You said that you know stats. I'm just wondering the probability of a couple of doctors understanding every aspect and component of how the body functions while everyone else is left behind. What are the chances of one person being able to indentify the cause of every symptom for every person, even though those symptoms are caused by different things in different people.So, what was the underlying cause of your disorders and symptoms?


> quote:majority of treatments are prescribed based on clinical evaluation of symptoms


 Again, true for IBS, but not for a lot of other stuff. Cancer isn't treated by a clinical evaluation of symptoms. In IBS the underlying disease process isn't understood, so how else would you do it? And again, what are the chances of a couple of doctors understanding this all while thousands of others can't?


> quote: the FDA and the pharma's have a poor track record. People are dying under their treatments. Why is it ok for us to accept the risk that a certain percentage of people will die under a given drug treatment.


 People die under every type of treatment, whether it be from the FDA, holistic medicine, a witch doctor etc. Just because a solution is "natural" does not mean it can't hurt you even if it is safer when considered as a whole versus another therapy.


> quote:there are ways for us to become well without this risk


 Again, every therapy involves risks. A simple nutrient like magnesium can do some nasty things if taken too much. Ephedra can cause decreased sweating and increased heartbeat. Even seeing a therapist can lead to unintended consequences. I could go on and on.


> quote: ALL OF IT fails to identify true cause of disease or functioning of the human body or interaction of all bodily processes


 I'd be a little scared if there was a 10 page manual that explains all the bodily processes. Hell, my microwave came with an instruction manual bigger than that. And still, what are the chances of one guy understanding the interaction of all bodily processes when no one else even understands a small percentage of them?


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## Jannybitt (Oct 13, 2006)

Eric;Apology accepted, and thank you. I appreciate that. You seem to be a very passionate person in your beliefs and of helping through what you learn. I know your heart is in the right place on this forum. Listen to your gut next time if it's telling you "not to take the bait"







Artjunky;You're welcome! And you are a real person that conveys things in a manner people can understand. And a very caring person too!!







Learning never stops! It's not supposed to! We'd get bored!


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## 16229 (Jan 28, 2006)

Thanks Jan.I just don't want to see people go through the same things that I did if they don't have to. I've learned so many hard lessons in life. If I can help someone see there is a way to live a productive life then at least I've done something good.People should do whatever they need to to find the solution that works for them. Confidence in care is just so important, people have to find someone they believe in to treat them.I don't think it is fair to label doctors and medical researchers as bums for lack of a better term. It's just not true. There are a lot of truly professional and good people out there working to make our lives better.


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## eric (Jul 8, 1999)

Good posts.







When we can calm down and discuss things it helps. IBS is one majorally complex disorder.It is also one reason why there is research. otherwise they would know all the answers.Basic science is starting to understand better the enteric nervous system and the bidirectional communication between the "gut brain (ENS) and the Brain and spinal cord or Central nervous sytem. CNSWhile doing so they learned the majority of serotonin 95% is stored in the gut and some of its actions in the bidirectional communication between the gut brain and the brain."Role of Serotonin in IBSDisruptions in integrated communications among the CNS, ANS, and ENS may contribute to the three key pathophysiological features of IBS: altered GI motility, visceral hypersensitivity, and altered intestinal secretion.[4] Numerous neurotransmitters and neuromodulators are involved in the communication between the IPANs and the effector systems (i.e., muscles and secretory and vascular cells) and in the mediation of bidirectional brain-gut communications. Serotonin appears to be the common link in GI motility, intestinal secretion, and pain perception and is involved at multiple levels in the bidirectional interactions between the ENS and the CNS; thus, it is considered to play an important role in the pathophysiological abnormalities observed in IBS.[4,38]"Very importantly it "Serotonin is directly involved in initiating the ENS-mediated peristaltic reflex""Serotonin and the Peristaltic ReflexSerotonin is directly involved in initiating the ENS-mediated peristaltic reflex (Figure 3).[3,45] Serotonin is released from EC cells in response to distention of the intestinal lumen (triggered by chemical or mechanical stimulation). Once released, serotonin interacts with 5-HT1p-receptors on the presynaptic nerve endings of the IPANs in the submucosal plexus. This initiates a cascade of events that facilitate the coordinated movement of the bowels. The signal from the 5-HT1p-receptors is communicated to 5-HT4-receptors located on the terminals of the submucosal IPANs. The 5-HT4-receptors then modulate peristaltic neurotransmission by facilitating the release of several neurotransmitters (e.g., acetylcholine and tachykinins) from these nerve cells, which results in muscle contractions proximal to the bolus and the release of other neurotransmitters (e.g., nitric oxide and vasoactive intestinal peptide), which in turn causes muscle relaxation distal to the bolus.[3,4,46-48] The net result is forward movement of the luminal contents through the GI tract."also"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_5This puts it a little more simplyHarvard"The Trusted Source..Harold J. DeMonaco, M.S.Harold J. DeMonaco, M.S., is senior analyst, Innovative Diagnostics and Therapeutics, and the chair of the Human Research Committee at the Massachusetts General Hospital. He is author of over 20 publications in the pharmacy and medical literature and routinely reviews manuscript submissions for eight medical journals...June 19, 2001.A:Irritable bowel syndrome is now recognized as a disorder of serotonin activity. Serotonin is a neurotransmitter in the brain that regulates sleep, mood (depression, anxiety), aggression, appetite, temperature, sexual behavior and pain sensation. Serotonin also acts as a neurotransmitter in the gastrointestinal tract.Excessive serotonin activity in the gastrointestinal system (enteric nervous system) is thought to cause the diarrhea of irritable-bowel syndrome. The enteric nervous system detects bowel distension (expansion) on the basis of pressure-sensitive cells in the bowel lumen (opening). Once activated, these pressure-sensitive cells promote the release of serotonin, which in turn promotes both secretory function and peristaltic function (the contractions of the intestines that force the contents outward). At least four serotonergic receptors have been identified to be participants in the secretory and peristaltic response.Patients with diarrhea-predominant IBS may have higher levels of serotonin after eating than do people without the disorder. This recognition led to the development of the first drug used specifically to treat diarrheal symptoms of IBS, alosetron (also known as Lotronex). Alosetron blocked the specific serotonin receptors responsible for recognizing bowel distention. In doing so, it blocked the effects of serotonin and reduced both bowel secretions and peristalsis. Constipation was the most common side effect seen. (Note: Alosetron was removed from the market by the manufacturer after repeated reports of a dangerous condition known as ischemic colitis became known.) Tegaserod (Zelmac) is another drug under development and under review by the U.S. Food and Drug Administration for approval. Tegaserod is indicated for the treatment of constipation-predominant IBS and works to increase enteric nervous system serotonin activity.So, increasing serotonin activity in the enteric nervous system produces increased bowel secretions and peristalsis (and potentially diarrhea), whereas depressing serotonin activity produces reduced secretions and reduce peristalsis (and potentially constipation). Increasing serotonin activity in the brain would increase awareness and, in higher doses, produce anxiety, insomnia and restlessness."However, the mechanisms are not fully understood because its so complex and other factors are also very important in IBS.But this has in part explain why there is abnormal motility in IBS the D and c and d/c, that there is a problem in serotnin singaling in the gi tract. The cells that store the majority of it in the gi tract, EC cells or enterochromaffin cells. In post infectious IBS, that is one of the abnormalities they found, an increase in enterochromaffin cells for one. Distinctive Features of Postinfective Irritable Bowel Syndrome "July 25, 2003 â€" Patients with postinfective irritable bowel syndrome (PI-IBS) have more diarrheal symptoms, fewer psychiatric symptoms, and a greater increase in serotonin-containing enterochromaffin (EC) cells than those whose IBS did not start after an infectious disease, according to the results of a study published in the July issue of the American Journal of Gastroenterology. The investigators speculate that subclassifying patients may allow for better and more specific therapies for some patients with IBS. "IBS patients are heterogeneous, both in symptoms and in etiology, and progress in understanding pathogenesis has been limited for lack of objective measures to allow meaningful subdivision," write Simon P. Dunlop, MSc, from University Hospital in Nottingham, U.K., and colleagues. "Recently there has been progress in defining one subgroup of patients, i.e., those developing IBS symptoms after an episode of infective gastroenteritis."They have also given rats a kind of IBS by messing with the EC cells.Serotonin is also cruical for signaling sensations and pain to the brain. However"Visceral Sensations and Brain-Gut MechanismsBy: Emeran A. Mayer, M.D., Professor of Medicine, Physiology and Psychiatry; Director, Center for Neurovisceral Sciences & Women's Health, David Geffen School of Medicine at UCLA"Our brain-gut axis is not designed to generate conscious perceptions of every alteration in gut homeostasis and internal environment, in particular when these changes are chronic, and when there is no adaptive behavioral response an affected organism could generate. Evolution has not designed our brain-gut axis to experience abdominal pain every time the number of mast cells in our ileum goes up, or the number of our serotonin containing cells goes down. It would be counter productive for an animal with a chronic parasite infestation to experience constant visceral pain, and it wouldn't have any advantage for people living in third world countries with frequent enteric infections to suffer from chronic abdominal pain. It has even been suggested that visceral pain may be a secondary phenomenon of an elaborate system of signaling non-painful signals to the brain: hunger, fullness (satiety), well-being after a meal, urge to evacuate, etc. At the same time, powerful mechanisms have evolved that keep many other aversive signals out of conscious perception: contractions, luminal distension, gas volume, low-grade inflammation, etc. The most common symptoms of IBS patients are related to altered perception of sensations arising from the GI tract, and frequently from sites outside the GI tract, such as the genitourinary system or the musculoskeletal system. Sensations of bloating, fullness, gas, incomplete rectal evacuation and crampy abdominal pain are the most common symptoms patients experience. Numerous reports have demonstrated that a significant percentage of FBD patients (about 60%) rate experimental distensions of the colon as uncomfortable at lower distension volumes or pressures when compared to healthy control subjects. This finding of an increased perception of visceral signals ("visceral hypersensitivity") has been demonstrated during balloon distension tests of the respective part of the GI tract regardless of where their primary symptoms are â€" the esophagus, the stomach, or the lower abdomen. In contrast to the current emphasis on mechanisms that may result in sensitization of visceral afferent pathways in the gut, it may well be that alterations in the way the nervous system normally suppresses the perception of the great majority of sensory activity arising from our viscera are essential for the typical symptom constellation of IBS and other functional GI disorders to develop."http://www.aboutibs.org/Publications/VisceralSensations.html


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## eric (Jul 8, 1999)

"What's New in the Management of IBS and Chronic Constipation? CMEDisclosuresBrian E. Lacy, MD, PhD IntroductionOver 10,000 physicians, scientists, researchers, and allied health personnel from around the world attended this year's Digestive Disease Week (DDW) meeting. Judging from the large number of oral presentations and posters, research on the etiology, pathophysiology, and treatment of functional bowel disorders continues at a rapid pace. This report reviews information presented during DDW 2006 with a focus on the clinically important lower gastrointestinal functional disorders of chronic constipation and irritable bowel syndrome (IBS)."Factors in EtiologyAlthough the precise etiology of IBS remains unknown, proposed mechanisms include genetic predisposition, inflammation, infection, stress, and psychological distress.[20] In addition, evidence now suggests that a deficiency in serotonin is associated with IBS with constipation, whereas excess serotonin is associated with IBS with diarrhea.http://www.medscape.com/viewarticle/536306MedGenMed GastroenterologyIBS -- Review and What's NewIntroductionIBS -- a complex, multifaceted condition broadly characterized by abdominal pain/discomfort associated with altered bowel habits -- is among the most prevalent gastrointestinal (GI) motility disorders. Prevalence estimates for IBS range from 3% to 20%, with most estimates in North America ranging from 10% to 15%.[1-3] Women are affected by IBS more often than men (2:1 in the community setting and 3:1 to 4:1 in the tertiary care setting).[2] IBS-related symptoms are often chronic and bothersome, negatively affecting patient activities of daily living (eg, sleep, leisure time), social relationships, and productivity at work or school.[4-6] Patients with IBS typically score lower than population norms or those with other chronic GI and non-GI disorders on measures of quality of life.[7-10] IBS also puts a heavy economic burden on patients, employers, and the healthcare system, resulting in more than $10 billion in direct costs (eg, from office visits, medications) and $20 billion in indirect costs (eg, through work absenteeism and reduced productivity) each year.[11-14]Advances in research during the past several decades have provided insight into the underlying pathophysiology of IBS, particularly the role of serotonin in the GI tract; the development of stepwise, symptom-based diagnostic strategies; and the development of targeted treatment options. This review discusses recent advances in research and explores how these findings can be applied in the clinical practice setting."The Science of IBSGiven the lack of definitive organic markers for IBS, the absence of a unifying hypothesis regarding its underlying pathophysiology is not surprising. Nevertheless, important advances in research made during the past 50 years have brought us closer than ever to understanding the numerous putative etiologic factors involved in this multifaceted disorder, including environmental factors, genetic links, previous infection, food intolerance, and abnormal serotonergic signaling in the GI tract.Environmental InfluencesAlthough a patient's psychological state may influence the way in which he or she presents, copes with illness, and responds to treatment, no evidence supports the theory that psychological disturbances are the cause of IBS.[39,40] The biopsychosocial model proposed by Engel takes into account the interplay between biologic, psychological, and social factors.[41] This model proposes that there is an underlying biologic predisposition for IBS that may be acted on by environmental factors and psychological stressors, which contribute to disease development, the patient's perception of illness, and impact on treatment outcomes.[42,43]Studies evaluating the role of acute stress have shown that stress can result in release of stress-related hormones that affect colonic sensorimotor function (eg, corticotropin-releasing factor [CRF] and inflammatory mediators [eg, interleukin (IL)-1]), leading to inflammation and altering GI motility and sensation.[44] For example, CRF-1 receptors located in the central nervous system (CNS) and gut can affect colonic motility, epithelial water transport, and gut permeability.[45] Sagami and colleagues[46] determined that the peripheral administration of a nonselective corticotropin-releasing hormone (CRH) receptor antagonist improved GI motility, visceral perception, and negative mood in response to gut stimulation in patients with IBS. These findings suggest that CRH may play an important role in the pathophysiology of IBS.GeneticsStudies with twins have shown that IBS is twice as prevalent in monozygotic twins as in dizygotic twins.[47-49] Limited research on familial aggregation has found that individuals who have a family member (other than a spouse) with a history of abdominal pain or bowel disorder have more than 2-fold increased odds of having IBS. It is likely that environmental influences may help explain this finding (eg, awareness of the symptom status of family members may make sufferers more open to discussing their symptoms and seeking help for the condition).[50] Preliminary findings also suggest that IBS may be associated with select gene polymorphisms, including those in IL-10, G-protein GNb3, alpha adrenoceptor, and serotonin reuptake transporter (SERT).[47, 51-54] Despite these potential links, however, conclusive evidence for a genetic basis for IBS has not been established.Postinfectious IBSThe presence of postinfectious (PI)-IBS, referring to the development of IBS symptoms -- particularly abdominal pain and diarrhea -- shortly after an enteric infection, is based on research from prospective studies in which IBS symptoms developed in 7% to 32% of patients after they recovered from bacterial gastroenteritis.[52,55,56] Specific risk factors for the development of PI-IBS have been identified, including younger age, female sex, presence of severe infectious gastroenteritis for a prolonged period, use of antibiotics to treat this infection, and presence of concomitant psychological disorders (eg, anxiety).[39,52,55,57] Difficulty in downregulating intestinal inflammation in the colonic mucosa has been suggested as a potential underlying mechanism in this condition.[52] Also suggested as a potential underlying mechanism is the presence of colonic changes shown in patients with PI-IBS compared with controls, including increased gut permeability, increased mucosal enterochromaffin cell production, and increased concentration of mast cells and T lymphocytes in the gut mucosa.[39,52,55,57] Despite considerable evidence linking IBS with an inflammatory etiology (perhaps triggered by enteric infection), in a controlled trial of patients with PI-IBS, anti-inflammatory treatment with prednisolone was not more effective than placebo in improving patient symptoms.[58] The true role of prior infection as a key factor in PI-IBS remains to be established.[59]The use of probiotics (products containing live or attenuated bacteria that have a positive effect on the host) in alleviating symptoms in patients with PI-IBS is an area of recent focus.[60,61] The potential utility of probiotics in this setting stems from their antibacterial, antiviral, and immune-modulating properties; their ability to modify intestinal flora; and their potential to enhance intestinal mucus secretion or influence stool consistency or volume and gas handling.[60] The number of studies evaluating the efficacy of probiotic preparations in patients with IBS is limited but growing.[60-68] Because trials vary in study design, dose, and strain (Lactobacillus and Bifidobacteria alone or in combination; mixture of Lactobacillus, Bifidobacteria, and Streptococcus), direct comparison of results is challenging. Overall, some degree of IBS symptom improvement has been demonstrated in symptoms such as abdominal pain,[65,66] bloating,[63,66] gas,[66] and daily symptom scores.[62,65] O'Mahoney and colleagues[60] have recently demonstrated that results with the Bifidobacterium infantis strain are particularly promising. In a separate analysis, these investigators showed that the baseline characteristics of urgency and hard stool increased the odds ratio of response to this strain, whereas straining and alcohol consumption reduced the likelihood of response.[69,70] The ultimate place in therapy of probiotics in IBS remains to be elucidated.Small Intestinal Bacterial OvergrowthThe presence of a higher than usual population of bacteria in the small intestine (leading to bacterial fermentation of poorly digestible starches and subsequent gas production) has been proposed as a potential etiologic factor in IBS.[71] Pimentel and colleagues have shown that, when measured by the lactose hydrogen breath test (LHBT), small intestinal bacterial overgrowth (SIBO) has been detected in 78% to 84% of patients with IBS.[71,72] However, the accuracy of the LHBT in testing for the presence of SIBO has been questioned.[73] Sensitivity of the LHBT for SIBO has been shown to be as low as 16.7%, and specificity approximately 70%.[74] Additionally, this test may suboptimally assess treatment response.[75] The glucose breath test has been shown to be a more reliable tool,[76] with a 75% sensitivity for SIBO[77] vs 39% with LHBT for the "double-peak" method of SIBO detection.[74] In a recently conducted retrospective study involving review of patient charts for the presence of gastrointestinal-related symptoms (including IBS) in patients who were referred for glucose hydrogen breath tests for SIBO, of 113 patients who met Rome II criteria for IBS, 11% tested positive for SIBO.[78] Thus, results demonstrated that IBS symptoms are often unrelated to the presence of SIBO. Despite the controversy regarding the contribution of SIBO to the underlying pathophysiology of IBS and its symptoms, short-term placebo-controlled clinical studies with select antibiotics, including neomycin and rifaximin, have demonstrated symptom improvement in IBS patients.[61,72,79] Antibiotics may therefore have potential utility in select subgroups of IBS patients in whom SIBO contributes to symptoms. However, the chronic nature of IBS symptoms often leads to the need for long-term treatment. Given the fact that long-term use of antibiotics is generally undesirable, the place of antibiotics in IBS therapy remains to be established.[73]Food IntoleranceFood intolerance has been proposed as a potential cause of GI symptoms in some patients with IBS; however, this link is not well established. Although some patients associate onset of IBS symptoms with ingestion of particular foods, identification of a true food intolerance is challenging, and elimination diets are typically time-consuming and difficult to implement. Recent research involving exclusion of foods to which patients had immunoglobulin (Ig) G antibodies, which are associated with a more delayed response after antigen exposure than IgE antibodies, resulted in significantly better symptom improvement than in patients in the nonexclusion group.[80] Further research into the role of food intolerance in IBS is warranted.*Serotonin Signaling* The effect of serotonergic mechanisms in the manifestation of IBS symptoms has led to development of a new drug class for the treatment of IBS patients: the GI serotonergic agents.Normal GI function relies on a properly functioning brain-gut axis, which involves the coordinated interplay of the GI musculature, the CNS, the autonomic nervous system, and the enteric nervous system (ENS). The ENS contains millions of neurons embedded in the wall of the digestive tract and functions, at least in part, independently of the CNS. The size, complexity, and independent function of the ENS has resulted in application of the terms "the second brain" and "the mini-brain."[81] Impaired function or coordination of any of these systems, or the communication between these systems and the GI musculature, can lead to symptoms of dysmotility and altered sensory perception, which are characteristic of IBS and select other GI motility disorders.[82]The neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) is a predominant signaling molecule in the ENS. Most (90% to 95%) of the body's serotonin is found in the gut, and smaller amounts are found in the brain (about 3%) and in platelets (about 2%).[83] In the GI tract, serotonin facilitates communication between the ENS and its effector systems (muscles, secretory endothelium, endocrine cells, and vasculature of the GI tract), thus playing a key role in normal GI tract functioning.[84] In addition, serotonin plays a role in the communication between the ENS and the CNS.In the gut, serotonin is synthesized by and stored in the enterochromaffin cells, which are located within the mucosa of the intestinal wall. When material passes through the lumen and the mucosa is stimulated, enterochromaffin cells release serotonin, which then binds to its receptors (primarily 5-HT1P receptors) on intrinsic primary afferent neurons, initiating peristalsis and secretion. Serotonin also binds to 5-HT4 receptors on interneurons, which augments the transmission of signals to motor neurons, resulting in enhanced peristaltic activity. In transgenic mice lacking 5-HT4 receptors, colonic motility is abnormally slow, confirming the role of these receptors in facilitating normal colonic motility.[85] By binding to 5-HT3 receptors on efferent sensory innervations coming from the vagus and the spinal nerves, serotonin mediates signaling between the ENS and the CNS and, thus, modulates pain perception.To regulate the signaling process, excess serotonin must be removed; this is accomplished by the SERT molecule expressed by intestinal epithelial cells.[86] Human studies have shown that defects in serotonin signaling contribute to the pathophysiology of IBS and, potentially, other GI motility disorders. In a recent study by Coates and colleagues,[87] biopsy specimens from patients with IBS showed significantly lower mucosal serotonin concentrations than those from healthy controls, potentially the result of lower mRNA levels for tryptophan hydroxylase (the rate-limiting enzyme in serotonin synthesis), which were also significantly lower in patients with inflammatory bowel disease.[87] There was no significant difference in the number of enterochromaffin cells or in the capacity of these cells to release serotonin under stimulated conditions. In another study, higher serotonin levels were observed in mucosal biopsy samples from patients with IBS with constipation (IBS-C) than in patients with IBS-D or in healthy volunteers.[88]Serotonin levels may also be affected by altering the amount or function of SERT. The study by Coates and colleagues[87] showed a significant decrease in the level of SERT mRNA and SERT protein expressed in the intestinal epithelial cells of IBS patients compared with that of healthy volunteers. In another study,[89] SERT expression and binding capacity in platelets were decreased in women with IBS-D compared with expression and binding capacity in healthy controls. Furthermore, Chen and colleagues[90] showed that mice with a SERT gene deletion had altered colonic motility. It is interesting to note that the mice thrived in laboratory housing conditions, indicating that other transporters could compensate for the lack of SERT. Additional studies have focused on SERT polymorphisms. Yeo and colleagues[91] showed an association between patients with IBS-D and the homozygous short polymorphism of the SERT gene promoter. This mutation results in lower levels of SERT gene transcription and reduced amounts of SERT protein available for reuptake of serotonin. In addition, Camilleri and colleagues[92] showed a possible link between the long promoter polymorphism and patient response to therapy.Thus, a substantially large body of work shows that normal gut physiology is predicated on the interplay between the GI musculature and the ENS, autonomic nervous system, and CNS. One of the central mediators of this complex interplay is the neurotransmitter serotonin. Impairment or imbalance in serotonergic signaling, which can affect GI motility, secretion, and visceral sensitivity, may be affected by defects or deficiencies in serotonin production, specific serotonin receptors, or proteins such as SERT. These changes can manifest in symptoms associated with IBS, including abdominal pain, altered bowel habits (constipation, diarrhea, or alternation between these 2 states), and bloating."http://www.medscape.com/viewarticle/532089_print


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