http://www.talkibs.org/impact_appendix.html
I found this site when the doctor explained the connection to me during one of our Q & A sessions! I asked - he really didn't answer - told me to research it on the net! Teehee
Here's a link to the sarotonin level
Moderators: Rosie, Stanz, Jean, CAMary, moremuscle, JFR, Dee, xet, Peggy, Matthew, Gabes-Apg, grannyh, Gloria, Mars, starfire, Polly, Joefnh
Here's a link to the sarotonin level
"Let us rise up and be thankful, for if we didn't learn a lot today, at least we learned a little, and if we didn't learn a little, at least we didn't get sick, and if we got sick, at least we didn't die; so, let us all be thankful." -- Buddha
I have an article on the gut/brain connection. let me see if I can find it.
Well, I don't have it on my hard drive. I will have to search for it on the Web. It's called Big Brain, Little Brain or something like that. I'll get back to you on this.
Love,
Sally
Well, I don't have it on my hard drive. I will have to search for it on the Web. It's called Big Brain, Little Brain or something like that. I'll get back to you on this.
Love,
Sally
Mitakuye oyasin
(Lakota for "We are all related")
(Lakota for "We are all related")
Here's a link to some information on the enteric nervous system:
http://www.hosppract.com/issues/1999/07/gershon.htm
I think you will find this discussion to be very interesting, regarding stress and the reactions of the enteric nervous system:
http://whyfiles.org/026fear/physio2.html
Love,
Wayne
http://www.hosppract.com/issues/1999/07/gershon.htm
I think you will find this discussion to be very interesting, regarding stress and the reactions of the enteric nervous system:
http://whyfiles.org/026fear/physio2.html
Love,
Wayne
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.
I cheated. Here's an interview with Dr. Gershon:
From Medscape Gastroenterology
Expert Interview
Advances in the Treatment of IBS With Diarrhea: An Expert Interview With Michael D. Gershon, MD
Posted 05/20/2004
Editor's Note:
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of demonstrable structural and biochemical abnormalities. The underlying pathophysiology of IBS is multifactorial and includes dysfunctions in intestinal motility and visceral sensitivity. These gastrointestinal abnormalities may be mediated by changes in the functions of the central nervous system and enteric nervous system. Indeed, serotonin signaling has been implicated in disease pathophysiology. Because this is a disorder marked by the absence of visible organic pathology, various symptom-based criteria are used to guide diagnosis. Therefore, symptom-based descriptions (eg, IBS with diarrhea) are applied to help guide management. Medscape spoke with Michael D. Gershon, MD, Professor and Chairman, Columbia University College of Physicians and Surgeons, New York, NY, and discussed the current state of the field in managing the patient with IBS with diarrhea, with consideration of the potential role of a novel 5-HT3 antagonist in this setting.
Medscape: What are the key challenges facing the physician treating the patient with IBS with diarrhea?
Michael D. Gershon, MD: IBS, with or without diarrhea, is a stable diagnosis;[1-3] therefore, the physician is likely to be dealing with a patient who either has become frustrated by an illness of long standing, or, if the diagnosis is made for the first time, by a patient who will become frustrated by a condition that the physician is not going to cure. The patient is also likely to have other complaints, which often include a functional disorder of the upper gastrointestinal tract, fibromyalgia, depression, or anxiety.[4-7] The challenge to the physician is to remain sympathetic and empathetic and not to become infected by the patient's frustration and/or depression. It will be necessary for the physician to not only tell the patient that IBS is a chronic condition of unknown origin that can be ameliorated but not cured, but to make clear to the patient that the disorder is a legitimate one and not the fault of the patient or evidence of the patient's mental state. The physician will then have to work through available therapies, starting with conventional treatments, none of which have even been demonstrated to be superior to placebos, and finally arrive at one that works, which for IBS with diarrhea will probably be a low dose of an antidepressant[1,5,8-12] or a 5-HT3 antagonist.[13-19]
Medscape: Serotonin signaling has been implicated in the pathophysiology of IBS. What therapeutic implications does this hold for the treatment of patients with IBS, and specifically IBS with diarrhea?
Michael D. Gershon, MD: The observation that there are molecular defects in the gut of patients with IBS (in the expression of the serotonin transporter and tryptophan hydroxylase-1)[20,21] elevates IBS to the status of other gastrointestinal disorders in which anatomic or chemical abnormalities can be found. Whatever the cause of these defects in the IBS bowel may be, their existence demonstrates that IBS exists in the gut and is not restricted to the patient's mind. This fact alone should be comforting to the physician as well as the patient. For patients with moderate or severe IBS with diarrhea, a physician is faced with a choice of prescribing a 5-HT3 antagonist that has clearly and repeatedly demonstrated efficacy but carries a risk of constipation,[13-19] or treating the patient with nostrums that may be safe but that have been tried for years without ever demonstrating their superiority to placebos. The 5-HT3 antagonists provide a rational approach to IBS that negates the detrimental effects of abnormal serotonergic signaling. Constipation, which is their major unwanted effect, is not life-threatening and, when anticipated, can be overcome by suspending treatment or lowering the dose. Ischemic colitis may also occur, but rarely,[22] and again should not be severe when a patient has been educated to look out for its symptoms.
Medscape: Cilansetron, a novel 5-HT3 antagonist, has demonstrated efficacy in providing adequate relief of IBS symptoms in nonconstipated men and women. What can you tell us about this agent and its potential role in this setting?
Michael D. Gershon, MD: The 5-HT3 receptors, which are the targets of cilansetron, are found on the terminals of extrinsic primary afferent neurons in the gut.[23-29] These axons transmit nociceptive signals to the central nervous system and, when these signals reach consciousness, they are universally unpleasant. The list of enteric sensations relieved by 5-HT3 antagonists -- nausea, pain, bloating, urgency -- is a paean to misery. The 5-HT3 antagonists, ondansetron and granisetron, have been approved by the US FDA and are extensively used to combat the nausea associated with cancer chemotherapy.[30] Another, 5-HT3 antagonist, alosetron, was, prior to its temporary withdrawal, effectively filling a niche in the treatment of IBS with diarrhea.[30] Alosetron was withdrawn because some patients who received it became severely constipated (approximately 1:1000) and ischemic colitis appeared in others (approximately 1:350).[15,16,19,22,31-33] Ischemic colitis occurs in patients with IBS and it is not clear that alosetron actually caused this problem.[22] The reapproval of alosetron by the US FDA occurred because of patient demand and is a testimony to how much relief the drug provided. Alosetron is now again on the market, but its acceptance has been limited by its prior history. Evidence suggests that cilansetron will be at least as effective as alosetron,[34,35] and in contrast to alosetron, which was only proven to be beneficial in women, cilansetron has demonstrated efficacy in men. Because 5-HT3 antagonists can worsen preexisting constipation, they should never be used in constipated men or women.
Medscape: Results of phase 3 efficacy studies with cilansetron were presented during this year's Digestive Disease Week meeting. Can you outline the key clinical findings in terms of patient benefit? How do you view the path forward in this field?
Michael D. Gershon, MD: The key clinical findings can be summed up by the word "effective." Cilansetron took on a placebo in a fair, double-blind, controlled challenge in the treatment of IBS and easily demonstrated superior efficacy. The compound works and it works in men as well as in women.[34,35] Conventional treatments for IBS with diarrhea cannot make this claim. IBS with diarrhea can be debilitating and even degrading to its sufferers. Cilansetron provides hope and a way out of the disabling grip of IBS for individuals who are severely or moderately affected. The chief unwanted effect experienced in the trials was constipation, which could be ameliorated by temporarily discontinuing treatment or lowering the drug dose, and often did not reoccur when therapy resumed. Ischemic colitis was encountered, but was rare and nonfatal. A head-to-head study of alosetron vs cilansetron has not been undertaken, nor has a prospective investigation been carried out to determine whether the incidence of ischemic colitis in nonconstipated patients with IBS treated with cilansetron is different from that in a comparable group of patients treated with conventional therapy, no therapy, or alosetron. As a result, it is not possible to know whether the risk of ischemic colitis (estimated to be 1:350 in patients receiving alosetron),[33] is increased by cilansetron; however, the risk is low and the benefit of the compound has been established.
In the future, more should be learned about why ischemic colitis occurs in a subset of patients with IBS, regardless of their treatment. It is possible that the association of ischemic colitis with IBS was only noticed in the first place because of the intense scrutiny given to patients in whom novel treatments were being analyzed. There is no current way to relate antagonism of 5-HT3 or any other 5-HT receptor subtype to the occurrence of ischemic colitis. A clearer understanding of the roles in intestinal physiology and pathophysiology of the very large number of different 5-HT receptor subtypes in the bowel is clearly needed and should be sought.
--------------------------------------------------------------------------------
Disclosure: Michael D. Gershon, MD, has reported that he has received grants for basic clinical research from Novartis. He also reported that he has served as an advisor or consultant for Solvay Pharmaceuticals. Dr. Gershon serves on the advisory board of EnteroMedics Incorporated, Theravance, Allergan, and SK Bio Pharmaceuticals.
From Medscape Gastroenterology
Expert Interview
Advances in the Treatment of IBS With Diarrhea: An Expert Interview With Michael D. Gershon, MD
Posted 05/20/2004
Editor's Note:
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of demonstrable structural and biochemical abnormalities. The underlying pathophysiology of IBS is multifactorial and includes dysfunctions in intestinal motility and visceral sensitivity. These gastrointestinal abnormalities may be mediated by changes in the functions of the central nervous system and enteric nervous system. Indeed, serotonin signaling has been implicated in disease pathophysiology. Because this is a disorder marked by the absence of visible organic pathology, various symptom-based criteria are used to guide diagnosis. Therefore, symptom-based descriptions (eg, IBS with diarrhea) are applied to help guide management. Medscape spoke with Michael D. Gershon, MD, Professor and Chairman, Columbia University College of Physicians and Surgeons, New York, NY, and discussed the current state of the field in managing the patient with IBS with diarrhea, with consideration of the potential role of a novel 5-HT3 antagonist in this setting.
Medscape: What are the key challenges facing the physician treating the patient with IBS with diarrhea?
Michael D. Gershon, MD: IBS, with or without diarrhea, is a stable diagnosis;[1-3] therefore, the physician is likely to be dealing with a patient who either has become frustrated by an illness of long standing, or, if the diagnosis is made for the first time, by a patient who will become frustrated by a condition that the physician is not going to cure. The patient is also likely to have other complaints, which often include a functional disorder of the upper gastrointestinal tract, fibromyalgia, depression, or anxiety.[4-7] The challenge to the physician is to remain sympathetic and empathetic and not to become infected by the patient's frustration and/or depression. It will be necessary for the physician to not only tell the patient that IBS is a chronic condition of unknown origin that can be ameliorated but not cured, but to make clear to the patient that the disorder is a legitimate one and not the fault of the patient or evidence of the patient's mental state. The physician will then have to work through available therapies, starting with conventional treatments, none of which have even been demonstrated to be superior to placebos, and finally arrive at one that works, which for IBS with diarrhea will probably be a low dose of an antidepressant[1,5,8-12] or a 5-HT3 antagonist.[13-19]
Medscape: Serotonin signaling has been implicated in the pathophysiology of IBS. What therapeutic implications does this hold for the treatment of patients with IBS, and specifically IBS with diarrhea?
Michael D. Gershon, MD: The observation that there are molecular defects in the gut of patients with IBS (in the expression of the serotonin transporter and tryptophan hydroxylase-1)[20,21] elevates IBS to the status of other gastrointestinal disorders in which anatomic or chemical abnormalities can be found. Whatever the cause of these defects in the IBS bowel may be, their existence demonstrates that IBS exists in the gut and is not restricted to the patient's mind. This fact alone should be comforting to the physician as well as the patient. For patients with moderate or severe IBS with diarrhea, a physician is faced with a choice of prescribing a 5-HT3 antagonist that has clearly and repeatedly demonstrated efficacy but carries a risk of constipation,[13-19] or treating the patient with nostrums that may be safe but that have been tried for years without ever demonstrating their superiority to placebos. The 5-HT3 antagonists provide a rational approach to IBS that negates the detrimental effects of abnormal serotonergic signaling. Constipation, which is their major unwanted effect, is not life-threatening and, when anticipated, can be overcome by suspending treatment or lowering the dose. Ischemic colitis may also occur, but rarely,[22] and again should not be severe when a patient has been educated to look out for its symptoms.
Medscape: Cilansetron, a novel 5-HT3 antagonist, has demonstrated efficacy in providing adequate relief of IBS symptoms in nonconstipated men and women. What can you tell us about this agent and its potential role in this setting?
Michael D. Gershon, MD: The 5-HT3 receptors, which are the targets of cilansetron, are found on the terminals of extrinsic primary afferent neurons in the gut.[23-29] These axons transmit nociceptive signals to the central nervous system and, when these signals reach consciousness, they are universally unpleasant. The list of enteric sensations relieved by 5-HT3 antagonists -- nausea, pain, bloating, urgency -- is a paean to misery. The 5-HT3 antagonists, ondansetron and granisetron, have been approved by the US FDA and are extensively used to combat the nausea associated with cancer chemotherapy.[30] Another, 5-HT3 antagonist, alosetron, was, prior to its temporary withdrawal, effectively filling a niche in the treatment of IBS with diarrhea.[30] Alosetron was withdrawn because some patients who received it became severely constipated (approximately 1:1000) and ischemic colitis appeared in others (approximately 1:350).[15,16,19,22,31-33] Ischemic colitis occurs in patients with IBS and it is not clear that alosetron actually caused this problem.[22] The reapproval of alosetron by the US FDA occurred because of patient demand and is a testimony to how much relief the drug provided. Alosetron is now again on the market, but its acceptance has been limited by its prior history. Evidence suggests that cilansetron will be at least as effective as alosetron,[34,35] and in contrast to alosetron, which was only proven to be beneficial in women, cilansetron has demonstrated efficacy in men. Because 5-HT3 antagonists can worsen preexisting constipation, they should never be used in constipated men or women.
Medscape: Results of phase 3 efficacy studies with cilansetron were presented during this year's Digestive Disease Week meeting. Can you outline the key clinical findings in terms of patient benefit? How do you view the path forward in this field?
Michael D. Gershon, MD: The key clinical findings can be summed up by the word "effective." Cilansetron took on a placebo in a fair, double-blind, controlled challenge in the treatment of IBS and easily demonstrated superior efficacy. The compound works and it works in men as well as in women.[34,35] Conventional treatments for IBS with diarrhea cannot make this claim. IBS with diarrhea can be debilitating and even degrading to its sufferers. Cilansetron provides hope and a way out of the disabling grip of IBS for individuals who are severely or moderately affected. The chief unwanted effect experienced in the trials was constipation, which could be ameliorated by temporarily discontinuing treatment or lowering the drug dose, and often did not reoccur when therapy resumed. Ischemic colitis was encountered, but was rare and nonfatal. A head-to-head study of alosetron vs cilansetron has not been undertaken, nor has a prospective investigation been carried out to determine whether the incidence of ischemic colitis in nonconstipated patients with IBS treated with cilansetron is different from that in a comparable group of patients treated with conventional therapy, no therapy, or alosetron. As a result, it is not possible to know whether the risk of ischemic colitis (estimated to be 1:350 in patients receiving alosetron),[33] is increased by cilansetron; however, the risk is low and the benefit of the compound has been established.
In the future, more should be learned about why ischemic colitis occurs in a subset of patients with IBS, regardless of their treatment. It is possible that the association of ischemic colitis with IBS was only noticed in the first place because of the intense scrutiny given to patients in whom novel treatments were being analyzed. There is no current way to relate antagonism of 5-HT3 or any other 5-HT receptor subtype to the occurrence of ischemic colitis. A clearer understanding of the roles in intestinal physiology and pathophysiology of the very large number of different 5-HT receptor subtypes in the bowel is clearly needed and should be sought.
--------------------------------------------------------------------------------
Disclosure: Michael D. Gershon, MD, has reported that he has received grants for basic clinical research from Novartis. He also reported that he has served as an advisor or consultant for Solvay Pharmaceuticals. Dr. Gershon serves on the advisory board of EnteroMedics Incorporated, Theravance, Allergan, and SK Bio Pharmaceuticals.
Mitakuye oyasin
(Lakota for "We are all related")
(Lakota for "We are all related")
Ok, the second link got me to reading more about histamines. I notice some of the symptoms found when histamines are present, and I also see some familiar foods here for folks. And since it seems that our immune systems are already overactive I bet that reactions to stress and diet containing histamines are exagerated.tex wrote:Here's a link to some information on the enteric nervous system:
http://www.hosppract.com/issues/1999/07/gershon.htm
I think you will find this discussion to be very interesting, regarding stress and the reactions of the enteric nervous system:
http://whyfiles.org/026fear/physio2.html
Love,
Wayne
When the brain signals danger, it tells so-called mast cells in the lining of the small intestine and/or colon to release histamine (defined) and other chemicals. These chemicals trigger an inflammatory response inside the small intestine, attracting immune cells from the bloodstream into the area. Voila, the body is ready for trauma, which often introduces dirty -- infectious -- material into the colon.
...
But when this inflammatory response gets out of whack, it can cause no end of problems -- things like irritable colon, a spasmodic condition that plagues its victims with diarrhea, gas and constipation; and ulcerative colitis, an inflammatory and disabling disease of the colon.
The enteric nervous system can explain other problems that are sometimes considered to be psychological in origin, like difficulty swallowing, ulcers and chronic abdominal pain.
Read more about here:Could you be histamine intolerant?
If you have at least two indicators of possible histamine intolerance symptoms shown below
Frequent headaches or migraines
Alcohol intolerance, esp red wine
Intolerance of yellow, hard cheese
Intolerance of sausages, salami, concentrated tomato products
Intolerance of chocolate
Chronic diarrhoea (not due to lactose or fructose intolerance)
Low blood pressure
rapid heartbeat, irregular heartbeat
Cramps on the 1st day of menstruation.
http://users.bigpond.net.au/allergydiet ... amine.html
Where histamines are here:
http://users.bigpond.net.au/allergydiet ... mines.html
Think I remember that article, Sally -- good one!
Need to review all the biochemical stuff, but I do have a sketchy model for how my migraines and IBS-type reactions to stress, and other secondary triggers were alike, and why both conditions responded to the elimination of the primary triggers, chief among which was gluten.
I once heard someone describe IBS as being like a seizure in the gut, and that lead me to realize that my longer problem with migraines was exactly like that -- a seizure. In fact, some with gluten sensitivity actually have seizures with it.
Simplistically, what I'm thinking happens is that the biochemical environment of the nerves that control the tissues involved are so sensitized that they become HIGHLY reactive to any stimuli, and thus, the electrical impulses are easily fired, and a cascade of symptoms is set in motion.
Guess now, I need to do some serious reading about what the biochemical environment would be that would set these events in motion.
I have a feeling that the IBS itself, much like the migraines, are only symptomatic of a higher order problem. My lifetime (almost) of migraines came to an abrupt halt with dietary treatment of the gs, etc. Obviously, the immune complexes are capable of damaging the immediate innervation, but then, they are also capable of damaging the higher centers of the brain, particularly once the damage is severe enough that the blood brain barrier is penetrated by the big immune complexes.
Do any of you want to venture a guess whether it was the damage to the brain centers or the more local nerves in both areas that were responsible for the "IBS" spasms and the migraines?
I do know that there's MUCH more serotonin activity in the gut than in the brain. This is one of the areas that, if I ever went back into research, I'd really love to study.
Also, the quick, sublingual, quick-dissolving migraine meds act by working on the serotonin, and they work well, let me tell you. Still, I don't think I'll ever need to take anything or that ever again.
Before I had those to take, until I finally vomited toward the end of the headache cycle, I'd not be able to get anything to come out, stool wise though it felt as though it needed to come out. Then, like magic, just as soon as I was through vomiting, the stool would come easily.
Now, I'm thinking that perhaps the same thing was happening as what I realized later was happening -- when I'd have a severe gluten reaction and the rectum would be sooo swollen that nothing would pass through, I'd assume it was constipation. This is when I could tell the 'rhoids were swollen as well. Come to think of it, if it'd been constipation, it would've looked like constipation when it came out immediately after the migraine symptoms left with the vomiting -- dah!
Sure would like to know the biochemistry and physiological mechanism for all this, and how it fits together.
Thanks the great sites. Will have to mail em to myself, and read later.
Yours, Luce
I once heard someone describe IBS as being like a seizure in the gut, and that lead me to realize that my longer problem with migraines was exactly like that -- a seizure. In fact, some with gluten sensitivity actually have seizures with it.
Simplistically, what I'm thinking happens is that the biochemical environment of the nerves that control the tissues involved are so sensitized that they become HIGHLY reactive to any stimuli, and thus, the electrical impulses are easily fired, and a cascade of symptoms is set in motion.
Guess now, I need to do some serious reading about what the biochemical environment would be that would set these events in motion.
I have a feeling that the IBS itself, much like the migraines, are only symptomatic of a higher order problem. My lifetime (almost) of migraines came to an abrupt halt with dietary treatment of the gs, etc. Obviously, the immune complexes are capable of damaging the immediate innervation, but then, they are also capable of damaging the higher centers of the brain, particularly once the damage is severe enough that the blood brain barrier is penetrated by the big immune complexes.
Do any of you want to venture a guess whether it was the damage to the brain centers or the more local nerves in both areas that were responsible for the "IBS" spasms and the migraines?
I do know that there's MUCH more serotonin activity in the gut than in the brain. This is one of the areas that, if I ever went back into research, I'd really love to study.
Also, the quick, sublingual, quick-dissolving migraine meds act by working on the serotonin, and they work well, let me tell you. Still, I don't think I'll ever need to take anything or that ever again.
Before I had those to take, until I finally vomited toward the end of the headache cycle, I'd not be able to get anything to come out, stool wise though it felt as though it needed to come out. Then, like magic, just as soon as I was through vomiting, the stool would come easily.
Now, I'm thinking that perhaps the same thing was happening as what I realized later was happening -- when I'd have a severe gluten reaction and the rectum would be sooo swollen that nothing would pass through, I'd assume it was constipation. This is when I could tell the 'rhoids were swollen as well. Come to think of it, if it'd been constipation, it would've looked like constipation when it came out immediately after the migraine symptoms left with the vomiting -- dah!
Sure would like to know the biochemistry and physiological mechanism for all this, and how it fits together.
Thanks the great sites. Will have to mail em to myself, and read later.
Yours, Luce