# The Hpa axis, Dr Sternberg, the immune system and IBS



## eric (Jul 8, 1999)

I am introducing something new to all this that is very important to IBS. Some of this is of course technical for sure, but interesting and a lot of research is being done on it for IBS and for inflammatory conditions and autoimmune conditions and a host of other conditions and dieases. It is called the HPA axis. It is a player in IBS and they are studying new drugs for it. I have been studying it for a while now and it is also a player in the immune system and stress and the stress responce and infection.First however I want to introduce really an international expert in the field of this and who she is as I feel that is very important.If you have some questions or comments shoot, although I have and am still learning. Her name isEsther M. Sternberg, M.D. Esther M. Sternberg, M.D., is Director of Integrative Neural Immune Program and Chief of the Section on Neuroendocrine Immunology and Behavior at the National Institute of Mental Health and National Institutes of Health. She was trained in rheumatology at McGill University and practiced medicine in Montreal before returning to a research career and teaching at Washington University in St. Louis. The winner of the Public Health Service Superior Service Award and President of the International Society for Neuroimmunomodulation, Dr. Sternberg has written over one hundred scientific papers, reviews, and book chapters on the subject of brain-immune connections, including articles in Scientific American and Nature Medicine. She has also co-directed an exhibition on Emotions and Disease at the National Library of Medicine and lectures nationally and internationally on emotions, health, and disease. Her groundbreaking book is "The Balalance within: The science of connecting health and emotions."I have not read it yet, but have read a lot of her work and am really looking forward to reading it. http://www.esthersternberg.com/ I am posting some online links to her work here including and audio you can listen to. Later I will go into how it is all tied into IBS.This is the first one with the audio and you have to click on the realplayer link to listen.







Its worth reading all the information on the pages also as it ties into so many conditions and is state of the art new science. http://www.akronroundtable.org/speakers/in..._sternberg.html The rest are papers online she has written.Does Stress Make You Sick and Believing Make You Well? The Science Connecting Body and Mind http://psydoc-fr.broca.inserm.fr/colloques.../Sternberg.html GET A GRIP ON STRESS http://www.healthatoz.com/atoz/healthupdat...rt06212001.html This last one is very very interesting and mentions 5htp (big in IBS) and an external skin condition. Among many other things. http://science-education.nih.gov/nihHTML/o...al/biomed1.html These things are tied into IBS in the immune system, stress hormones, stress responce, infections ect., but I will say more on that later.I found this all really interesting myself I hope all of you do.


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## Guest (Nov 10, 2002)

Sounds good, Eric. If I weren't on my way out for the evening I would read it now. Thank youEvie


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## eric (Jul 8, 1999)

Evie, I hope you and others get a chance to review all this, its actually a very important part of IBS.I am going to say more about it on IBS and you will be hearing more about it from the research in IBS.


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## ohnometo (Sep 20, 2001)

Thanks for the articles..I read them and I am trying to keep an open mind..I know I am going to hear alot about this in January when I see Dr Fleisher..so I will start by reading over and over about stress and how it can effect us







I have read some articles that he has wrote about stress and out systems..Not sure I agree yet..but maybe I will in the next few months


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## eric (Jul 8, 1999)

This system I am talking about here seems to be major in IBS, but they are researching it. Its still important that there is a phyical problem in the gut and that serotonin is not regulating right in IBS at the gut receptor levels. However it might be the reason why this system then plays such a big part also.Donna, did you listen to the audio?Also here is something for you or who ever might be interested.Encyclopedia of Stress http://www.apnet.com/stress/ This is extremely technical but a talk of her's on IBS and these processes. http://www.conference-cast.com/ibs/Lecture...fm?LectureID=13 These are two UCLA article's just released from their IBS center.Heartburn and stress. http://www.med.ucla.edu/ndp/Newsletters/Summer02Hrtbrn.htm The autonomic nervous system. This system controls digestion. http://www.med.ucla.edu/ndp/Newsletters/Summer02ANS.htm Dr Mayer is a very respected neurogastroenterologists and also an important person researching IBS.There site which has a lot of IBS info. http://www.med.ucla.edu/ndp/NwsltrIndex.htm Altred stress responces in IBS. This has info on the hpa axis and IBS http://www.med.ucla.edu/ndp/Newsletters/Wi...teredStress.htm A pubmed abstract.Am J Med 1999 Nov 8;107 5A:12S-19S Emerging disease model for functional gastrointestinal disorders. Mayer EA. Division of Digestive Diseases, University of California Los Angeles School of Medicine, USA. In response to perceived or experienced change that is considered threatening to the individual, the central nervous system mounts a stereotypic response that decreases the sensitivity to pain, modulates the autonomic nervous system outflow, and activates the hypothalamic-pituitary-adrenal HPA axis. This response of the "emotional motor system" may or may not be associated with the conscious experience of feelings of fear or anxiety. Alterations in these response systems either up- or downregulation may produce symptoms, such as viscero-somatic hypersensitivity, altered bowel habits, or increased anxiety. Publication Types: Review Review, Tutorial PMID: 10588168Last the new emerging eveidence for very microscopic inflammation in the gut, they are trying to figure out also and the info I posted above is part of this. The hpa axis is a player in infection."A LINK BETWEEN INFLAMMATION AND STRESS An increase in inflammatory mediators alone is insufficient to explain the pathogenesis of IBS. From post-infective IBS, we know that the most people who have gastroenteritis and accompanying inflammation do not develop IBS. As discussed earlier, several factors may be important in interacting with the gut insult and in predicting those who develop symptoms - one interesting factor here is the role of stress. Psychological stress is known to affect gut function in normal healthy humans, and in people with IBS stress may trigger or exacerbate symptoms. More recently there is evidence of a link between stress and inflammatory responses. Exposure to stress in both animals and humans has been shown to result in the release of mast cell mediators in the colon18,19 and in a recent study stress was capable reactivating previous inflammation in rats15. An important challenge for future work will be to clarify the interaction between inflammation, stress and IBS symptoms." http://www.med.unc.edu/medicine/fgidc/infl...rymediators.htm


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## LML (Jul 17, 2001)

Great stuff, Eric. Thanks so much for sharingall this info. Although I can't pretend to understand all the details, it makes so much sense. And there's an exciting comfort in knowing that there's such good research happening makingthese connections. I look forward to learning more and hopefully learning how to address some of these ideas to my own conditions in time. Hope is a great thing!Linda


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## eric (Jul 8, 1999)

LML, I am glad your looking it all over. I am not posting it hopefully to confuse people. It is very hard to understand it all and some extremely technical, but a little at a time and just knowing about it can help.I know it can make your head hurt. LOLIts good to know there are some extremely smart people helpinng us for the future to cure "maybe" or at least make this non existent symptoms wise which would be a cure for the most part.I am gonna start a new thread soon on people/doctors who are helping us and this is just a few of them. I think it also helps when your looking for some accurate information on IBS.Its also helps to show this is all connected mind and body. Gut brain axis ect..When you start learning about the different nervous systems, the brain gut axis and the functions of neurotransmitters ect, it make things you do or try to manage IBS make more sense also and just understanding some of this somewhat can be a huge help. IBS is just so flippin complicated. I don't think people need to be experts on it completely, although I think it helps to know as much about a condition yoou have as possible because knowledge is power over it, but I really believe knowing some basics can really help. Most people I know with IBS in my support groups and things who are new to learning, might not understand the brain in the gut ENS enteric nervous system and how it applies to their IBS but its very important.


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## eric (Jul 8, 1999)

Actually LML, basically there are two systems that seem to be a problem in IBS causing the symptoms for the most part or at least what they know up to this point.The serotonin loop from the brain to the gut and back and the HPA axis, are both players. Not that other things are not players also, but these two seem to be big ones.


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## eric (Jul 8, 1999)

This is some more with Dr Mayer work again from a couple years ago. Again technical, but somewhat understandable I hope.







http://www.macmcm.com/pcp/pcp2000_01.htm These two cells are very important in IBS and they release serotonin for one.mast cells, enterochromaffin cells, the later stores most of the serotonin in the gut. They have found increases of these cells in IBSers."Serotonin: A Mediator of the Brain-Gut Axis Jackie D. Wood, PhD (Ohio State University) characterized the enteric nervous system as "the little brain in the gut" and as the lower end-point of the hierarchical innervation of the GI tract. The other components are prevertebral sympathetic ganglia, central sympathetic centers in the brainstem, central parasympathetics (the dorsal-vagal complex) where the vagus nerve and the descending pathways of the spinal cord originate, and higher brain centers (e.g., prefrontal cortex, amygdala, parabrachial nucleus, and hypothalamus). The sympathetics and parasympathetics are descending pathways to the gut. The higher brain centers interact with the autonomic centers by sharing information on perceptions of GI sensations and mani- festations of psychogenic factors such as physical and emotional stress. The chemical transfer of information within this circuitry is the work of serotonin (5-hydroxytryptamine, or 5-HT), 95 percent of which is localized in the GI tract and the remainder in the brain and enteric nervous system. In the first, an action potential traveling along an axon triggers release of the neurotransmitter (neurocrine signaling) 5-HT, carrying the signal to the post-synaptic neuron. In the second, 5-HT is released by either an enteric mast cell or an enterochromaffin cell (paracrine signaling). This affects neurons by extracellular diffusion. Whether by neurocrine or paracrine release, 5-HT excites neurons by inducing rapidly activating depolarization or slowly activating depolarization of the membrane potential. The 5-HT3 receptor is involved in rapidly activating depolarization. These receptors are located on the terminals of vagal afferent sensory neurons. They are activated by triggering the release of 5-HT. The activated vagal afferent transmits information in the form of action potential codes to the central nervous system. This mechanism is the peripheral basis of nausea and vomiting and the reason for using 5-HT3 antagonists as antiemetic drugs. Similarly, 5-HT3 receptors located in spinal (splanchnic) afferents are involved in signaling the central nervous system with information on the state of the gut. If these become sensitized during inflammation, elevated postprandial 5-HT serum levels may induce an exaggerated sensory code that goes into spinal integrated circuits and may reach the level of consciousness as discomfort or pain. Mast cells execute sensitization reactions to food or infection by releasing 5-HT and other mediators such as histamine. The 5-HT1P and 5-HT4 receptors modulate hypersensitivity reactions of the gut such as hypersecretion and propulsive motor events. Presynaptic inhibition (possibly through 5-HT4 receptors) at a nicotinic synapse is an important mechanism by which 5-HT affects enteric function. In addition, the 5-HT4 receptor facilitates release of acetylcholine at nicotinic synapses. This underlies the augmented intestinal propulsion seen with some prokinetic drugs. In general, motor, sensory, and chemical stimuli precipitate the release of 5-HT, which binds with sub-types of 5-HT receptors in the vagal sensory and splanchnic nerves, producing a variety of effects on the peristaltic reflex, colonic tone (5-HT3), acceleration of pan-gut transit (5-HT4), and gastric accommodation (5-HT4 and 5-HT1A). New 5-HT agents are being used experimentally to determine the roles of 5-HT receptor sub-types in motor and sensory function in the GI tract. Tegaserod and prucalopride are 5-HT4 agonists that appear to affect propulsion, and cisapride is simultaneously a 5-HT4 agonist and 5-HT3 antagonist that improves gastric accommodation. Dogiel type II myenteric neurons have a special gating function in the enteric nervous system. Unless stimulated by 5-HT, these multipolar neurons maintain a state of low excitability. But both neurocrine and paracrine release of 5-HT transforms them to a state of high excitability. Stimulation of the 5-HT receptors on their mucosal processes spreads action potentials up toward the cell body in the myenteric plexus. Once the cell body is activated, it gates the activity to other places in the enteric nervous system setting off a variety of secretory and motor events. Like enterochromaffin cells, intestinal mast cells are a source of 5-HT. These become sensitized in food allergies and infections by specific antibodies that adhere to receptors on their cell surfaces. Reappearance of the antigen cross-links the antibodies, causing degranulation of the mast cells and release of 5-HT and a variety of other mediators. The result is a form of gut behavior that includes hypersecretion and very strong propulsive contractions with attendant symptoms of diarrhea and abdominal discomfort. This behavior is programmed by the enteric nervous system and organized to eliminate threatening agents from the bowel lumen rapidly. Involvement of 5-HT1 and 5-HT2 receptors in the dorsal vagal complex has an apparent role in the brain-gut axis and psychogenic elements of bowel disorders of function. Laboratory experiments have shown that injection of spinal fluid into the fourth ventricle to influence the dorsal vagal complex produces no motility response. Injection of 5-HT alone stimulates motility minimally. But microinjection of thyrotrophin-releasing hormone followed by 5-HT generates an accentuated motility effect and acid secretion." http://www.macmcm.com/acg/acg99_gdf.htm


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## trbell (Nov 1, 2000)

it does look like they are pinning down the emotional role here and Freud was right all along, doesn't it. see newsweek this week. i don't know if it's on the internet yet.tom


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## eric (Jul 8, 1999)

I am just adding this as its very important to this all.Homeostasis http://pespmc1.vub.ac.be/HOMEOSTA.html


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## eric (Jul 8, 1999)

A step back some years to 97.UCLA Breakthroughs in IBS research.This is part of all of this. http://www.med.ucla.edu/ndp/Newsletters/Spring97Break.htm


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## LML (Jul 17, 2001)

Eric, thanks again for getting this info all together. As an artist, I deal with conceptual ideas. My daughter, with a biological sciencebackground, is going to spend some time helping me understand the mechanics of this. In a couple weeks I'll see if I can distill some of this into coherent thoughts for a non-scientific type. And you're so right about knowledge about a situation or condition contributing to better peace of mind. Linda


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## Guest (Nov 13, 2002)

There is no doubt in my mind about the connections being made in the articles Eric. (There is definitely an autoimmune connection for me.) Tom, I think you know where I stand on this. Body, brain and mind...... they're all connected.I often think the reason I have not been "done in" or why I can keep on keepin' on is because even when I am in the throes of the deepest depression.... I fight as hard as I can with as much positive energy as I can.... to defeat this "beast" that wants (but will never have) complete control of my body, brain and mind.Evie


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