Irritable Bowel Syndrome Message Boards | Comprehensive video from stanford univ. on ibs causes

They have already demonstrated PI IBS as a brain gut axis disorder.

This is one reason why not all people with an enteric infection develop IBS.

The CRF is anotheer issue with the brain and signals coming from the gut. The gut singals the brain and the brain realeases CRF and signals back to the gut. This is part of the HPA axis responce. It singals mast cells in the gut and they release histimine unto the smooth muscle and that contributes to the pain.

Readers' Exchange
Defining Stress in IBS
Fall 2003

From Arizona -- Thank you so much for your efforts and support for those of us with GI disorders. Your first issue (Spring 2003) of Digestive Health Matters is both professional and informative. I would like to comment on one of the articles - "The CNS: Center for Neurovisceral Sciences and Women's Health at UCLA." I am encouraged to know that steps are being taken for funding research of IBS and interstitial cystitis. However, it is discouraging that researchers are still expending time and money to research "neurobiological mechanisms by which stress modulates brain-visceral interaction." I realize that stress is a popular theory in the discussion of IBS triggers, however, I believe this is completely backward and it is the chronic pain and totally unreliable bowel function of an IBS sufferer which causes the greatest stress. If research would focus on "fixing" the bowel, no doubt the panic and fear of IBS would be greatly alleviated.

Comment from Emeran A. Mayer, M.D. -- In contrast to the common interpretation of the term "stress" as a psychological phenomenon, it should be understood as any real or perceived perturbation of an organism's homeostasis, or state of harmony or balance. For example, in this viewpoint a severe hemorrhage, starvation, extreme temperature, or worry about the unpredictable onset of abdominal pain all qualify as stressors -- some as "physical" stressors, others as "psychological" stressors. The fear to leave the house in the morning without knowing if one can make it to work without having to stop on the freeway because of an uncontrollable bowel movement, or the fear of experiencing uncontrollable abdominal discomfort during an important business meeting are sufficient stressors to activate the central stress system.

The central stress system involves the release of chemical stress mediators in the brain (such as corticotropin releasing factor), which in turn orchestrate an integrated autonomic, behavioral, neuroendocrine, and pain modulatory response. This biological response in turn will alter the way the brain and the viscera interact, and this altered brain-gut interaction can result in worsening of IBS symptoms. Thus, pain and discomfort, fear of these symptoms, activation of the stress response, and modulation of the brain-gut interactions by stress mediators are part of a vicious cycle which need to be interrupted to produce symptom relief.

The neurobiology of stress is not a theory, but a topic that can be studied in animal models, and one of the hottest topics in drug development for treatment of IBS (e.g., substance P antagonists, corticotropin releasing factor antagonists).

Merck Manual

"In this disorder, the digestive tract is especially sensitive to many stimuli. Stress, diet, drugs, hormones, or minor irritants may cause the digestive tract to contract abnormally, usually leading to diarrhea. Periods of constipation may occur between bouts of diarrhea. Irritable bowel syndrome affects women 3 times more often than men.

The brain has enormous control over the digestive system. Stress, anxiety, depression, fear, and virtually any strong emotion can lead to diarrhea, constipation, and other changes in bowel function and can further worsen a flare-up (bout or attack) of irritable bowel syndrome."

http://www.merck.com...129/ch129d.html

Dr Wood's comments for me

"Dr. Jack Wood, a renowned physiologist at The Ohio State University calls the ENS the little-brain-in-the-gut.

"Dear Shawn:

Sorry for the delayed reply to your question. I generally agree with Dr. Drosssman's response. A subgroup of individuals when they become sensitized to specific molecules in certain foods respond to ingestion of the molecules with symptoms of cramping abdominal pain, fecal urgency and explosive watery diarrhea. These are also the primary symptoms of diarrhea-predominant IBS. Enteric mast cells, by mechanisms we don't understand, become sensitized to the food molecule and respond to its presence by releasing a signal to the brain-in-the-gut (ENS) which is interpreted as a threat. The ENS responds by running a program which organizes secretion and motility into a behavior pattern of the bowel, which rapidly clears the threat from the lumen. Because to be effective secretion occurs in large volumes and the contractions that accomplish rapid propulsion are strong, running of the program has the side effects of diarrhea and cramping pain.

Big brain input to mast cells during stress activates the mast cells to evoke the symptoms resulting from exposure of the mast cells to sensitizing food antigens. Aside from food allergens and mast cells, certain chemicals such as those in hot peppers, stimulate sensory nerves in the ENS and we are beginning to understand how this can also lead to food-related symptoms that might mimic or exacerbate IBS.

Hope this helps,

Jackie (Jack) D. Wood "

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 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."

So two majorally important cells in the gut are enterochromaffin cells and mast cells. The enterochromaffin cells or EC cells release serotonin to start gut contractions. This process helps explain d and c and d/c.

The alteration in the gut is seen as a "threat" by the brain and the brain's hpa axis is then activated.

These cells are embedded in the lining of the gut brain and are close to each other.

IN PI IBS they have found an increase of both these cells embedded in the gut.

"By using sophisticated imaging techniques that allow us to visualize the activity of the living human brain (see “Looking Into the Living Human Brain”), researchers at the UCLA Neuroenteric Disease Section have recently identified for the first time the regions within the brain that are involved in the perception and modulation of visceral sensations, including visceral pain. In addition, by comparing brain responses to an acute intestinal stimulus between healthy control subjects, patients suffering from IBS, and patients with ulcerative colitis, they were able to identify specific alterations in how the brains of IBS patients process and respond to acute colonic pain."

History of functional disorders.

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 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, 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.

BRAIN-GUT AXIS
The 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, ccc 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.

med.unc.edu/medicine/fgidc/historyfunctionaldisorders.pdf

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My website on IBS is www.ibshealth.com

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Its part of the brain-gut dysfunction theory. The gut first singals the brain and the brain signals the gut. But the gut can upset the brain and the brain can upset the gut.

One thing to note here, is inflammation cannot be a biomarker in IBS, because it doesn't always cause pain. All people with celiac sprue have inflammation, but not all of them have pain.

This is something that all the people in thrid world countries who get enteric gut infections all don't get PI IBS. There are important issues that make people more likely to get PI IBS.

This was from 2004 from the same center at ucla and DR Mayer.

Minerva Med. 2004 Oct;95(5):419-26.

The pathophysiology of irritable bowel syndrome.
Schwetz I, Bradesi S, Mayer EA.

Center of Neurovisceral Sciences and Women's Health (CNS), Division of Digestive Diseases and Brain Research Institute, Department of Medicine, Los Angeles, CA, USA.

Abstract
Recent studies have provided evidence to suggest a possible role for mucosal immune activation in the pathophysiology of irritable bowel syndrome (IBS). On the other hand, novel findings using functional brain-imaging techniques support the concept that altered perception of visceral stimuli plays a key role in IBS symptom generation. These seemingly contradictory findings have revived the discussion about the relative contribution of peripheral versus central mechanisms in the symptom generation of IBS. In this review, we will provide evidence for the hypothesis that, in the absence of changes in visceral perception and alterations in endogenous pain modulation systems, chronic inflammatory mucosal changes in the gut are not a plausible mechanism to explain the presence of chronic abdominal pain, a clinical hallmark of IBS.

So its not inflammation that is a "plausible mechanism" for pain in IBS. And the "changes in visceral perception and alterations in endogenous pain modulation systems" by the brain are believe to be essential to pain in IBS.

Normal digestion in IBS can cause pain, but not in normals and all pain is of course processed in the brain.

The CRF is generated from the HPA axis and is a top down issue from a responce to the top up issues. But it doesn't make either one less important, because both are going on and causing symptoms and both can be treated.

The hypothalamic-pituitary-adrenal axis (HPA or HTPA axis), also known as the limbic-hypothalamic-pituitary-adrenal axis (LHPA axis) and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland (a pea-shaped structure located below the hypothalamus), and the adrenal (or suprarenal) glands (small, conical organs on top of the kidneys). The interactions among these organs constitute the HPA axis, a major part of the neuroendocrine system that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood and emotions, sexuality, and energy storage and expenditure.

Its a major part of the bodies stress responce and reaction, but also helps fight infections and pathogens in the gut. This is in part why they see macroscopic inflammation of specific cells in the gut and the surrounding tissue.

But mast cells are just one of the problems, there is much more evidence for serotonin dysregulation from ec cells.

The point here is it is more effective to treat both the brain and the gut for the best outcomes, because they are both operational to cause the symptoms. Some of this is like the domino effect.

This might be interesting as well. Dr Mayer responds in this to a study from the UNC. They are basically on the same page and collaborate with each center.

Pain Sensitivity in Irritable Bowel Syndrome (IBS) Study
What causes pain sensitivity in IBS patients?
An article by Spencer D. Dorn, M.D. et al published in the journal Gut (2007;56;1202-1209) entitled, "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?

In this summary and commentary, clinician and researcher Emeran A. Mayer, M.D. offers a different perspective. Following Dr. Mayer's comments, Spencer D. Dorn, M.D. and William E. Whitehead, Ph.D., two authors of the study, respond. Finally, we add an editorial comment.

Summary and Commentary by Emeran A. Mayer, M.D.
The study by Dorn and a group of experienced investigators is a well designed and executed research study of 121 patients with irritable bowel syndrome (IBS) and 28 healthy control subjects. The goal of the study was to determine if the characteristic increased perception of experimental colorectal distension ("visceral hypersensitivity") reported by many laboratories around the world is due to "physiological or psychological factors."

The authors studied the patient's subjective response to inflation of a balloon placed into the lower part of the bowel/colon, according to two well established distension protocols. One of these is thought to measure the "objective" sensitivity of the neural pathways, and the other to measure the respective tendency of an individual to "report" pain, regardless of actual neural sensitivity.

The authors confirmed previous reports that IBS patients as a group report pain and urgency (feeling the need to have a bowel movement) at significantly lower colonic distension pressures than healthy control subjects. However, using a technique called sensory decision theory (SDT) analysis, they failed to demonstrate differences in "objective" sensitivity; IBS patients and control subjects showed similar sensitivity of the neural pathways mediating the sensations of pain and urgency. The authors provide evidence that the observed lower perception thresholds for pain and urgency are fully accounted for by "an increased tendency to report pain." In addition, they show that this increased reporting tendency is weakly, but statistically significantly, correlated with psychological measures, such as somatization (frequently described as the physical expression of psychological problems) and general psychological distress.

Based on their findings the authors conclude that the increased perception of colonic distension in IBS patients is strongly influenced by a greater psychological tendency to report pain rather than a "real" physiological hypersensitivity.

Commentary
Even though this is an interesting and important study, the conceptual model and hypotheses on which the study is based are very limited and result in a message to investigators and physicians, to the public, and particularly to affected patients, which is highly problematic. I would like to point out the most striking of these problems.

1.The human pain experience is multidimensional. It is influenced by a variety of factors, including input from sensory nerve pathways, cognitive and emotional factors, the general homeostatic state of the organism, and by recall of past memories and experiences. This "deconstruction" of the human pain experiences into its multiple neurobiological dimensions has only recently become possible using sophisticated neuroimaging techniques of the brain. At the level of the brain, there is no distinction between psychological and physiological mechanisms (a main hypothesis of the authors is that there is such a distinction). Even though some aspects of the pain experience are generated in the brain by limbic circuits (such as arousal or anxiety) and others by cortical pathways (such as belief systems and coping skills) all pain dimensions are generated by neurobiological activity.
2.Unless one measures the electrical activity of sensory nerves during a painful stimulus, or looks directly at the brain activity using electroencephalographic (EEG) or neuroimaging techniques it is difficult to measure objective "neurosensory sensitivity" from subjective stimulus ratings. Any time a pain measure relies on the subjective response of a subject, it is the product of the multiple dimensions outlined in the paragraph above. Thus the study by Dorn is based on the debatable concept that any objective, neurological assessment of pain or non-painful sensations can be derived from subjective patients' responses (as opposed to direct neurological recordings of nerve or brain activity).
3.The conclusion that IBS patients don't have "real" hypersensitivity but that their subjective discomfort and ultimately symptoms are to blame on their "greater tendency to report pain" is also a problematic interpretation of their findings. Convincing evidence has been provided by several research groups that IBS patients show greater anxiety in expectation of potentially aversive stimuli to the gut or to the lower abdomen, and that this so called symptom related anxiety may play an important role in central pain amplification [increasing the pain sensation in the central nervous system] and ultimately in symptoms. Recent brain imaging studies, which visualize brain activity, have identified the biological brain circuits and mechanisms that play a role in this anticipatory anxiety, and in its role in central pain amplification. This is not a psychological (e.g., non-physiological) phenomenon, but is a dysregulation in neurobiological mechanisms related to pain sensitivity.
In summary, this is an interesting and well executed paper, which puts into serious question the concept that the enhanced perception (commonly referred to as "visceral hyperalgesia") is related to the peripheral sensitization of visceral afferent pathways (nerve pathways from the gut), for example by some type of immune activation in the gut. However, it is unfortunate that the main findings and conclusions of this article are likely to nurture the still prevailing prejudice, that IBS patients like to complain about symptoms that are not real, and that this tendency is a reflection of their psychological problems. As long as we continue to divide symptoms into those that are psychological in nature, and therefore not as real as those that are physiological and organic, we will never understand some of the most common and burdensome chronic illnesses such as IBS, depression, and chronic pain syndromes.

� Emeran A. Mayer, M.D., Professor of Medicine, Physiology, Psychiatry & Biobehavioral Sciences; Director, Center for Neurovisceral Sciences & Women's Health, David Geffen School of Medicine at UCLA, Los Angeles, CA

Authors' Reply to Dr. Mayer: Better Understanding of the Pain Experience May Lead to Better Treatment
Dr. Mayer is critical of the methods we used to study the pain experiences of IBS patients and suggests that neuroimaging of the brain may have advantages over our techniques. We will give our views of these alternative methods for studying pain below. However, the most important issue, as the last paragraph of Dr. Mayer's commentary makes clear, is his concern that our study findings might harm IBS patients by reinforcing the prejudices of some physicians that IBS is "only" a psychological disorder. We share the concern that readers might jump to simplistic conclusions rather than trying to understand the complexity of the pain experience. However, we carried out and published our study in the belief that, in the long run, well conducted research will benefit IBS patients by leading to more appropriate treatments, even though the research findings may seem unpopular at first.

Dr. Mayer acknowledges that the human pain experience is influenced by a variety of factors that include sensory nerve pathways, cognitive and emotional factors, and past memories and experiences. However, he argues that this complexity cannot be studied by techniques such as sensory decision theory which analyze the ways patients describe their subjective experiences in response to pain stimuli; he argues that only sophisticated neuroimaging of the brain can achieve this. While we agree that functional brain imaging (i.e., identifying which areas of the brain become more active in response to pain sensations from the bowel) is an important new method for increasing our understanding of visceral pain, we do not believe it has achieved the precision of methods such as sensory decision theory as yet. Not enough is known about what specific parts of the brain do, and it is clear that brain activation reflects a mixture of sensory, cognitive, and emotional influences. This makes it difficult to disentangle different influences on the pain experience. Sensory decision theory and other techniques of cognitive science, on the other hand, have a long developmental history, and the meaning of the findings is well worked out.

Dr. Mayer is critical of our assumption that it is useful to distinguish between physiological and psychological contributions to pain. We believe that this distinction is important; we believe, for example, that it is important to distinguish the influence on pain of a recent attack of gastroenteritis from the effects of fear and expectancy because these different causes of pain are likely to require very different treatments. We agree with Dr. Mayer that psychological processes have a biological basis (namely the electrical impulses in neurons), and that psychological processes therefore influence which parts of the brain are most active. The problem, in our view, is that examining images of brain activation does not as yet allow us to distinguish between physiological factors such as gastroenteritis and psychological factors such as worrying about whether we have cancer. Such distinctions are important, and they are readily appreciated by asking patients to report about their subjective experiences.

Our findings are supportive of other recent research on visceral pain and how to go about relieving it. Dr. Mayer notes that several research groups including his own have shown that anxiety related to the expectation of abdominal pain plays an important role in central pain amplification and ultimately in symptoms. That is the conclusion of our study.

We do not believe, nor do we imply, that IBS patients are falsely reporting what they experience. However, our study shows that IBS patients are no better at telling the difference between two intensities of pain than anyone else, and they tend to label unpleasant sensations as painful at lower intensities than most other people. This is not unique to patients with IBS; it has been observed in patients with other chronic pain conditions. We believe this is important because it makes a difference in which treatments are likely to benefit patients with IBS. These observations may be difficult to understand or even uncomfortable to accept, but our conviction is that knowledge brings power for good.

� Spencer Dorn, M.D., and William E. Whitehead, Ph.D., University of North Carolina Center for Functional GI and Motility Disorders, Chapel Hill, NC

Editors' Comment � a Final Note
We think it is important that any article about a study of the perception of pain in IBS be sensitive to the long history of negative attribution aimed at the IBS patient. That the disorder is "all in their head" remains a popular notion. Reuters reporting the Dorn study under the angle, "Pain sensitivity in IBS patients may be psychological," helps perpetuate that notion.

Despite the educational efforts of professional groups such as the Rome committees and of advocacy groups such as IFFGD, misconceptions persist that IBS is not "legitimate." Or that it's a nuisance � or that the patients are a nuisance. The satirist/commentator Bill Maher, on a 2006 segment of the TV show, Real Time with Bill Maher, said: "I mean, it seems as if every time I turn on the TV these days, I see some ad for some drug I never heard of to treat some disease I never heard of. That's not a stomach ache you have from eating the chili-cheese fries at Johnny Rockets, it's Irritable Bowel Syndrome. Or IBS. Or as I call it, BS." A similar opinion by Maher was published in an op-ed piece in the Los Angeles Times. Attitudes like this seem rooted in society. They spill over into the normal support channels for people with IBS, including their family members and even clinicians. What's more, they affect attitudes among regulators and funding agencies.

Perhaps it should not be surprising that Bill Maher and others have never heard of IBS; it's a disorder that most sufferers have a hard time talking about. But perpetuating misconceptions about the disorder will only reinforce the desire to keep silent about it, making it even harder for people with IBS to find proper care.

We know that pain is perceived in the brain, and that a host of emotional and cognitive factors interplay with stimulus to create that perception. It is important to keep in mind that these influences on pain may not distinguish individuals with IBS from those with other chronic pain conditions. (Published studies have compared IBS patients with control groups of healthy individuals.) As Drs. Dorn and Whitehead say in their response above, "(labeling) unpleasant sensations as painful at lower intensities than most other people is not unique to patients with IBS; it has been observed in patients with other chronic pain conditions."

Well designed studies avoid factors that would bias results. But when talking about IBS, it is the audience that is likely biased. We think researchers promoting understanding of the disorder need to consider that bias when reporting their findings. An explanation in the Dorn article of how humans, with or without IBS, process pain would have provided perspective that may have helped avoid, in effect, shining a spotlight on the IBS patient as if they are somehow different.

It is extraordinary that IBS researchers, pursuing scientific explanations to help a population of suffering people, must also explain that this suffering is real. But it seems to yet be necessary.

� William F. Norton, Publications Editor, IFFGD

I think we are basically on the same page as well Syl, just looking at it a little differently. This is the first study to show actual structural difference in the brain of IBS patients, although all women. So it has important ramifications to all IBS research.

This was from one of the chats with the experts. Part of the point I am trying to make.

"Psychophysiological arousal is the core of treating functional gi disorders. There is so much distress, anxiety, antisipatory anxiety, and negative reaction to symptoms, that calming the mind and body often makes a significant difference to symptoms."

Reagardless of where all the problems/biomarkers may lie.

This is a more holitic approach to the whole person and the symptoms.

If I am not mistaken Dr Mayer believes there is a problem with how the brain is responding to signals from the gut and the bidirectional communication between the gut brain and brain. They are so closely intertwined they look at them as all part of the same system. They have found problems in both the gut and the brain now.

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My website on IBS is www.ibshealth.com

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