[bonniei]

This is my understanding of IBS. Is this correct?That serotonin reuptake at the receptors is the problem.That there seems to be fewer serotonin transporters(SERT) than normal to help in the reuptake around these receptors. That serotonin more than normal around these receptors in the gut is the problem. For it accelerate the transit. This leads to IBS-D. While much more than normal serotonin leads to receptor desensetization so that reuptake just doesn't happen and completely blocks the peristaltic reflex and leads to IBS-C. While the ebb and flow of the amount of serotonin leads to alternation between diarrhea and constipation

 

[Nath]

Thats basically it as far as I understand it. If its the actual cause or if its a result of some other fault is still up in the air, as far as I know.

 

[bonniei]

Thank you for responding. I guess since none of the experts have disputed it it must be correct.

 

[overitnow]

Why would SRIs be useful if all cases show higher than normal serotonin?

 

[bonniei]

First of all SRI's target different receptors than 5HT3 and 5Ht4. So that could make a difference. Now if you have IBS D or IBS C then reuptaking the extra serotonin is necessary since in both cases the serotonin is higher,. In IBS-C it is much higher than IBS-D

 

[eric]

J Clin Gastroenterol. 2005 May-Jun;39(4):S184-93. Related Articles, Links Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome.Gershon MD.From the Department of Anatomy and Cell Biology, Columbia University, P&S, New York, NY.The bowel exhibits reflexes in the absence of CNS input. To do so, epithelial sensory transducers, such as enterochromaffin (EC) cells, activate the mucosal processes of intrinsic (IPANs) and extrinsic primary afferent (sensory) neurons. EC cells secrete serotonin (5-HT) in response to mucosal stimuli. Submucosal IPANs, which secrete acetylcholine and calcitonin gene-related peptide, initiate peristaltic and secretory reflexes and are activated via "5-HT1P" receptors. Release of neurotransmitters is enhanced by 5-HT4 receptors, which are presynaptic and strengthen neurotransmission in prokinetic pathways. 5-HT3 receptors mediate signaling to the CNS and thus ameliorate cancer chemotherapy-associated nausea and the visceral hypersensitivity of diarrhea-predominant irritable bowel syndrome (IBS-D); however, because 5-HT3 receptors also mediate fast ENS neurotransmission and activate myenteric IPANs, they may be constipating. 5-HT4 agonists are prokinetic and relieve discomfort and constipation in IBS-C and chronic constipation. 5-HT4 agonists do not initiate peristaltic and secretory reflexes but strengthen pathways that are naturally activated. Serotonergic signaling in the mucosa and the ENS is terminated by a transmembrane 5-HT transporter, SERT. Mucosal SERT and tryptophan hydroxylase-1 expression are decreased in experimental inflammation, IBS-C, IBS-D, and ulcerative colitis. Potentiation of 5-HT due to the SERT decrease could account for the discomfort and diarrhea of IBS-D, while receptor desensitization may cause constipation. Similar symptoms are seen in transgenic mice that lack SERT. The loss of mucosal SERT may thus contribute to IBS pathogenesis.PMID: 15798484Am J Health Syst Pharm. 2005 Apr 1;62(7):700-11. Related Articles, Links Rationale for using serotonergic agents to treat irritable bowel syndrome.Baker DE.College of Pharmacy, Washington State University, P.O. Box 1495, Spokane, WA 99210-1495. bakerdan###wsu.edu.PURPOSE: The role of serotonin in gastrointestinal (GI)-tract functioning, the pharmacologic rationale for using serotonergic agents in the treatment of irritable bowel syndrome (IBS), and clinical experience with novel serotonergic agents are described. SUMMARY: IBS is a common multisymptom disorder that is associated with a high socioeconomic burden. The goal of treatment is to provide rapid and sustained global relief of the multiple symptoms of IBS with a single, effective, well-tolerated agent. Traditional treatment options target single symptoms, and many patients are dissatisfied with the level of relief achieved and adverse effects. Research has revealed that serotonin is involved in three major actions in the gut: (1) mediating intestinal motility, (2) mediating intestinal secretion in the GI tract, and (3) modulating perception in the bowels. Serotonin is also a vital link in the brain-gut axis. Alterations in key elements of serotonin signaling have been demonstrated in patients with IBS. Tegaserod, a selective serotonin type 4 (5-HT(4))-receptor partial agonist, is indicated for use in women with IBS whose primary bowel symptom is constipation. Alosetron, a 5-HT(3)-receptor antagonist, is indicated for use in women with severe diarrhea-predominant IBS in whom traditional therapies have failed. The clinical usefulness of several other serotonergic agents for IBS is being investigated. CONCLUSION: The use of serotonergic agents in patients with IBS is based on the critical role that serotonin plays in the maintenance of normal gut function and brain-gut communication. Pharmacologic therapies targeting specific serotonin receptors represent an important step in the management of IBS.PMID: 15790796

 

[Kathleen M.]

http://www.anaesthetist.com/anaes/patient/ans/ens.htmHas a good basic overview of how the stuff works in the Enteric Nervous system and explains how SSRI's have some of the GI effects that they have.http://www.gastro-pro.org/index.html?http&...ibs/ibs-03.html has a good overview of various things with IBS. It is an interview rather than a paper so some things may be oversimplified

 

[bonniei]

quote:Of interest is the rapid re-uptake of serotonin at nerve terminals, limiting its action. This physiology provides a good explanation for the nausea and diarrhoea commonly seen when selective serotonin reuptake inhibitors (SSRI) are used to treat depression.

http://www.anaesthetist.com/anaes/patient/ans/ens.htmI wonder what this means? Does "limiting its action" mean that it stops reuptaking it after a while so that too much serotonin accumulates and causes D?

 

[bonniei]

Oh overitnow I completely missed the "I" in SSRI. .It means to inhibit the reuptake. So then how does it prevent diarrhea if all that excess serotonin is floating around? So my question is the same as yours. But I think there was a thread on it a few years ago which dealt with the topic, so I will review it and get back to you.Secondly I can answer the question in the last post. When all the serotonin is reuptaken, there is no serotonin to act and hence its action is limited. So infact SSRIs since they inhibit the reuptakre of serotonin, lead to too much serotonin lying around and this leads to the side effect of diarrhea. It seems to me SSRI's will be good for constipation as diarrhea is a desired side effect.

 

[bonniei]

Here is how Remeron which is useful for controlling Diarrhea works"The first of a new class of drugs, Remeron does not broadly block the reuptake of norepinephrine or serotonin like other SSRIs. Instead, Remeron stimulates the release of norepinephrine and serotonin, while blocking certain receptors that have been linked with lowered sex drive, nausea, nervousness, headache, insomnia, and diarrhea."http://www.healthyplace.com/communities/de...depressants.aspI hope it is clear now, overitnow. Sorry for my initial mistake.

 

[Kathleen M.]

Once the serotoin is "reuptaked" the serotonin is no longer doing anything because it is sequestered back inside a cell.Remeron is a "setron" like Lotronex. It is not a traditional SSRI.K.

 

[bonniei]

Yes there are many types of SSRIs. Whether they work for you depends on on what type of IS you have and what its particular actions are. It may be doing more than just reuptaking serotonin, like blocking receptors which are linked to diarhhea or constipation although I haven't found any which block receptors that are linked to constipation although if normal people don't have too much of serotonin, then if the reuptake is inhibited by SSRI, it could lead to just enough serotonin to cause diarrhea in them. Or even lead to alternation. I don't know if SSRI's are used for IBS-C because one of the criticisms of it is that it causes severe C. overitnow or anyone else if you give me a particular SSRI used for constipation, maybe then I can find more info

 

[bonniei]

Ok I found this"Fluoxetine(Prozac) has been shown to decrease orocecal and whole gut transit times in both constipation-predominant IBS and controls (11). This may explain why Tabas et al. observed some benefits in terms of constipation in their trial (4). Venlafaxine (Effexor)(an inhibitor of serotonin and norepinephrine reuptake) has been shown to reduce colonic compliance and relax the colon in healthy volunteers (12). " So looks like these might help constipation but this is due to actions other than getting too much serotonin in the gut around the 5HT3 and 5HT4 recptors.

 

[paul762]

I think prozac caused my IBS-D, I stopped taking them suddenly after 3 months, and from then on have gradually got worse, nothing is helping at present, had blood tests, all normal, so now got to have a colonoscopy, when I book it !

 

[bonniei]

paul, it is quite possible that it led to D and then you got anxious about the D and anxiety and D got linked, so now you have anxiety related D. I don't think taking Prozac causes a permanent disturbance of the serotonin system but long term effects of SSRIs have not been studied so who knows.

 

[paul762]

normally I would agree, however I have been left with other symptoms other than IBS-D, which were not symptoms at the time, which lead me to believe that there is a possible connection, eg. ticks, extreme yawning, biting teeth hard together. these things only came about being on prozac and none have gone away after almost two years after stopping the drug. talking to the gp that prescribed them is useless, as she will have no intention of taking any sort of blame. but what can you do ?

 

[bonniei]

Well i don't think you are supposed to stopProzac suddenly. And it is possible that thee are side effects of the med.

 

[eric]

Am J Health Syst Pharm. 2005 Apr 1;62(7):700-11. Related Articles, Links Rationale for using serotonergic agents to treat irritable bowel syndrome.Baker DE.College of Pharmacy, Washington State University, P.O. Box 1495, Spokane, WA 99210-1495. bakerdan###wsu.edu.PURPOSE: The role of serotonin in gastrointestinal (GI)-tract functioning, the pharmacologic rationale for using serotonergic agents in the treatment of irritable bowel syndrome (IBS), and clinical experience with novel serotonergic agents are described. SUMMARY: IBS is a common multisymptom disorder that is associated with a high socioeconomic burden. The goal of treatment is to provide rapid and sustained global relief of the multiple symptoms of IBS with a single, effective, well-tolerated agent. Traditional treatment options target single symptoms, and many patients are dissatisfied with the level of relief achieved and adverse effects. Research has revealed that serotonin is involved in three major actions in the gut: (1) mediating intestinal motility, (2) mediating intestinal secretion in the GI tract, and (3) modulating perception in the bowels. Serotonin is also a vital link in the brain-gut axis. Alterations in key elements of serotonin signaling have been demonstrated in patients with IBS. Tegaserod, a selective serotonin type 4 (5-HT(4))-receptor partial agonist, is indicated for use in women with IBS whose primary bowel symptom is constipation. Alosetron, a 5-HT(3)-receptor antagonist, is indicated for use in women with severe diarrhea-predominant IBS in whom traditional therapies have failed. The clinical usefulness of several other serotonergic agents for IBS is being investigated. CONCLUSION: The use of serotonergic agents in patients with IBS is based on the critical role that serotonin plays in the maintenance of normal gut function and brain-gut communication. Pharmacologic therapies targeting specific serotonin receptors represent an important step in the management of IBS.PMID: 15790796 Clin Gastroenterol Hepatol. 2005 Apr;3(4):349-57. Related Articles, Links Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome.Dunlop SP, Coleman NS, Blackshaw E, Perkins AC, Singh G, Marsden CA, Spiller RC.Background & Aims: 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists improve symptoms in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 5-HT 4 agonists help those with constipation-predominant IBS (C-IBS). These data suggest excess or deficiency in 5-HT in D-IBS or C-IBS, respectively. Mucosal 5-HT-containing enterochromaffin cells (EC) are increased in postinfectious IBS (PI-IBS). Our aim was to define the postprandial release of 5-HT in PI-IBS and C-IBS patients and to relate this to mucosal 5-HT turnover. Methods: Fifteen PI-IBS patients with diarrhea-predominant symptoms, 15 C-IBS patients, and 15 healthy controls underwent serial (platelet-poor) plasma 5-HT measurement for 3 hours after a standard 520-kcal meal. Rectal biopsy specimens were assayed for 5-HT and its metabolite 5-hydroxindoleacetic acid (5-HIAA). Colonic transit was measured using radio-opaque markers. Results: Colonic transit was prolonged in C-IBS patients (mean +/- SEM) (49.4 +/- 3.8 h) compared with PI-IBS (26.7 +/- 4.5) and control patients (34.1 +/- 4.5) ( P < .02). Release of 5-HT assessed by area under the curve (AUC) of platelet-poor plasma 5-HT from 0 to 180 minutes postprandially was significantly lower in C-IBS patients (2593 +/- 309 mmol/L . min) compared with P-IBS (5623 +/- 721) and control patients (4822 +/- 598) ( P < .001). PI-IBS patients showed significantly higher peak postprandial plasma 5-HT values (median, range) (71.7, 43.4-125.3) ng/L compared with C-IBS patients (31.2, 15.2-40.5) and control patients (43.6, 26.7-50.1) ( P < .01). Mucosal 5-HT turnover as assessed by mucosal 5-HIAA/5-HT ratio was decreased in both C-IBS and PI-IBS patients, .14 (.01-.6) and .21 (.02-2.5), respectively, compared with control patients 1.12 (.17-3.1) ( P < .002). Conclusions: C-IBS patients show impaired postprandial 5-HT release whereas PI-IBS patients have higher peak levels, abnormalities that may be related to their different symptoms.PMID: 15822040

 

[18548]

this might be completely off track but would it be possible that researchers are going wrong thinking of IBS as a single syndrome and that perhaps it is more like an umbrella of very similar things, like colitis and crohn's are both IBDs? That could explain why they aren't getting any regular patterns with their tests etc. Also can someone please explain how antidepressants can help if the problem is a raised amount of seratonin? i thought they increased production?

 

[bonniei]

Not all antidepressants raise serotonin. THE SSRIs, seotonin reuptake inhibitors, which as the name suggests reduce the reuptake of serotonin near the receptors leading to more serotonin around them. Serotonin around the 5HT3 and 5HT4 receptors leads to diarrhea in excess and in even more excess leads to constipation. THE SSRIs lead to more serotonin around the 5HT1 and 5HT2 receptors and this does not seem to affect bowel movements. Secondly remeron, a SSRI, blocks the receptors which are linked to diarrhea and helps in that way. Prozac decreases the time for the transit of food and perhaps in that sense helps constipation. So they help independently of their action on their main targets 5HT and 5HT2 receptors.