Serotonin is a major player in IBS, but more in the gut then in the brain.
95 percent of serotonin in the body is stored in the gut.
It maynot be the enitre answer in IBS, but it is one of the problems.
Relaxation techniques boost serotonin levels in the brain also.
However, in IBS its not that there is to much or to little its that it is not regulating the way it should be between the gut and the brain and back, and right now there is research looking at gut cells in the digestive system that sotre it and release it for digestion. There looks like there is a problem there.
However, because this is all so complicated they still have a lot more work to do. However, a lot of basic science has also gone into this research.
Release Date: 10-22-2003
UVM Researchers Identify Molecular Changes in IBS Patients
Author: Jennifer Nachbur
Email: Jennifer.Nachbur@uvm.edu
Phone: (802)656-7875 Fax: (802) 656-3203
Novel research shows that alterations in serotonin signaling in the gastrointestinal (GI) tract are present in patients with Irritable Bowel Syndrome (IBS). These data shed light on the alterations in gut motility, secretion, sensation, as well as the clinical manifestations of IBS, which include abdominal discomfort, pain, bloating, constipation and/or diarrhea.
The study findings were presented last week by two lead investigators from the University of Vermont, Peter Moses, M.D., Associate Professor of Medicine and Director of Clinical Research in the Digestive Diseases, and Gary Mawe, Ph.D., Professor of Anatomy and Neurobiology, in an oral presentation during the plenary session at the 68th Annual Scientific Meeting of the American College of Gastroenterology in Baltimore.
"Serotonin is a critical signaling molecule necessary for normal gut function – when released, it causes gut motility and secretion, and triggers signals to the brain and spinal cord," said Moses. "Our finding that key elements of serotonin signaling are changed in IBS lends credibility to the notion that IBS is not simply a psychological or social disorder as was once thought, but instead due to altered gut biochemistry and interactions between the gut and the brain."
Serotonin (5-HT) is a naturally occurring neurotransmitter and signaling molecule. Ninety-five percent of all serotonin is localized in the GI tract where it plays a key role in the motor, sensory and secretory functions of the gut. For some time, scientists have suspected that alterations in serotonin may contribute to abnormal conditions in the GI tract.
"Now we have a perspective on molecular changes in the intestines of individuals with IBS that we did not have before," said Mawe. "We identified a significant decrease in the serotonin transporter in cells that form the inner lining of the bowel – the same serotonin transporter that is located in cells in the brain. In the gut, this transporter acts as a sponge to remove serotonin once it is released, and therefore stops its actions. Because the transporter is diminished in IBS, serotonin stays around longer, and this can lead to changes in motility, secretion and sensitivity."
The study examined tissue obtained from 43 healthy controls and 32 patients with IBS and 22 patients with inflammatory bowel disease (IBD). IBS patients were defined strictly using ROME II criteria. Each biopsy was evaluated by five parameters: immunohistochemical staining, histological assessment, serotonin content, serotonin release and the measurement of mRNA encoding. The study also examined the molecular components of serotonin signaling, including the serotonin re-uptake system. Specifically, the investigators measured serotonin content, the endocrine cell number, serotonin release and presence of serotonin transporters (SERT). Serotonin transporters are regulatory molecules that control the activity of serotonin within nerve endings in the GI tract to coordinate motility, visceral sensitivity and intestinal secretion.
In patients with IBS, the study found a significant decrease in serotonin content and significantly higher endocrine cell (EC) populations in patients with IBS compared to controls, while the release of serotonin from EC cells was not significantly different. In terms of the way the body inactivates serotonin signaling, or the serotonin re-uptake system, SERT mRNA and SERT immunoreactivity were markedly reduced. This reduction led to a decrease in the capacity to remove serotonin from intracellular space once it was released, thus increasing serotonin availability.
http://www.uvm.edu/news/print/?action=Print&storyID=4188
This study was sponsored by a drug company, but a ton of work now has been ongoing on the role of serotonin and IBS. Its important not to just dismiss it because it was a drug company study. Because tons of work has been done on this and connections with serotonin.
almost all IBSers presenting to gastroenterologists, effectively demonstarte serotonin dyregulation of the serotonin system.
The act of eating in IBS d patients, shows and increase of serotonin which causes the bowel to overreact.
Serotonin Signaling and Visceral Hypersensitivity in IBS
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FYI
From Medscape Gastroenterology
MEDLINE Abstracts: Serotonin Signaling and Visceral Hypersensitivity in IBS
Posted 10/23/2003
What's new concerning the role of serotonin signaling and mechanisms of visceral hypersensitivity in the pathophysiology of irritable bowel syndrome (IBS)? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Gastroenterology.
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Serotonin and Its Implication for the Management of Irritable Bowel Syndrome
Gershon MD
Rev Gastroenterol Disord. 2003;3(suppl 2):S25-S34
Our understanding of the enteric nervous system (ENS) has evolved from the "classical" view, in which the brain controls all enteric behavior, to the current view, which holds that enteric innervation is one of local control within the bowel, modified by a bidirectional "dialogue" with the brain. The ENS independently controls enteric reflexes through intrinsic primary afferent neurons, which monitor intraluminal conditions. This monitoring is accomplished through the use of enteroendocrine cells in the mucosa, the best known of which are the serotonin-containing enterochromaffin cells. This article describes the roles that serotonin, specific serotonin-receptor subtypes, and the serotonin reuptake transporter play in the ENS and in the communication between the ENS and central nervous system. The way in which these findings have implicated serotonin in irritable bowel syndrome is discussed.
Systematic Review: Serotonergic Modulators in the Treatment of Irritable Bowel Syndrome--Influence on Psychiatric and Gastrointestinal Symptoms
Kilkens TO, Honig A, Rozendaal N, Van Nieuwenhoven MA, Brummer RJ
Aliment Pharmacol Ther. 2003 ;17:43-51
Background: Both central and peripheral serotonergic modulators are used in the treatment of irritable bowel syndrome. The majority of patients with irritable bowel syndrome presenting to a gastroenterologist demonstrate affective dysregulation. Serotonin may play a regulatory role in both gastrointestinal motility and sensitivity, as well as in affective dysregulation, in irritable bowel syndrome.
Aim: To analyse, systematically, randomized controlled trials studying the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome, in order to elucidate baseline irritable bowel syndrome symptomatology and possible differential effects of serotonergic modulation on this symptomatology.
Methods: A standardized qualitative analysis was performed of studies investigating the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome using a blind review approach. The studies were ranked according to their total quality score (maximum 100 points).
Results: Eleven studies fulfilled the entry criteria, six of which scored above 55 points. An association between gastroenterological and psychiatric changes was present in five of the six studies.
Conclusions: The results strengthen the serotonergic association between gastroenterological and psychiatric symptoms. Adjusted guidelines for combined gastrointestinal and psychiatric assessments are recommended in order to further elucidate the serotonergic interaction between gastrointestinal and psychiatric symptoms.
Tegaserod and Other Serotonergic Agents: What Is the Evidence?
Chey WD
Rev Gastroenterol Disord. 2003;3(suppl 2):S35-S40
Through effects on gastrointestinal motor and secretory function as well as visceral sensation, serotonin (5-HT) plays a key role in the pathogenesis of irritable bowel syndrome (IBS). In particular, 5-HT3 and 5-HT4 receptors appear to be very important in IBS. This article critically appraises the evidence supporting the use of the 5-HT3 receptor antagonist alosetron in the treatment of women with diarrhea-predominant IBS. The safety profile and restricted-use program for alosetron is also reviewed. This discussion is followed by a comprehensive review of the efficacy and safety data in support of tegaserod for women with constipation-predominant IBS.
Sex Differences of Brain Serotonin Synthesis in Patients With Irritable Bowel Syndrome Using Alpha-[11C]Methyl-L-Tryptophan, Positron Emission Tomography and Statistical Parametric Mapping
Nakai A, Kumakura Y, Boivin M, et al
Can J Gastroenterol. 2003;17:191-196
Background: Irritable bowel syndrome (IBS) is the most common functional bowel disorder and has a strong predominance in women. Recent data suggest that the brain may play an important role in the pathophysiology of IBS in the brain-gut axis. It is strongly suspected that serotonin (5-HT), a neurotransmitter found in the brain and gut, may be related to the pathophysiology of IBS. It is reported that a 5-HT3 antagonist is effective only in female patients with diarrhea-predominant IBS.
Objective: In the present study, 5-HT synthesis was measured using positron emission tomography, with alpha-[11C]methyl-L-tryptophan as the tracer, in patients with IBS. The aim of the present study was to compare 5-HT synthesis in the IBS patients with that in the controls, and to compare 5-HT synthesis between male and female IBS patients.
Methods: Six male and six female nonconstipated IBS patients were scanned. Age-matched healthy volunteers were scanned as controls. Eighty minute dynamic scans were performed. Functional 5-HT synthesis images were analyzed using statistical parametric mapping.
Results: 5-HT synthesis was greater only in the female IBS patients in the right medial temporal gyrus (multimodal sensory association cortex) compared with the female controls (P<0.001).
Conclusions: The greater brain 5-HT synthesis in the female IBS patients than in the controls may be related to the pathological visceral pain processing of the IBS patients, a larger female predominance of the disorder, and the sex difference of the efficacy of the 5-HT3 antagonist in treatment.
Sex-Related Differences in IBS Patients: Central Processing of Visceral Stimuli
Naliboff BD, Berman S, Chang L, et al
Gastroenterology. 2003;124:1738-1747
Background & Aims: Women have a higher prevalence of irritable bowel syndrome (IBS) and possible differences in response to treatment, suggesting sex-related differences in underlying pathophysiology. The aim of this study was to determine possible sex-related differences in brain responses to a visceral and a psychological stressor in IBS.
Methods: Regional cerebral blood flow measurements using H(2)(15)O positron emission tomography were compared across 23 female and 19 male nonconstipated patients with IBS during a visceral stimulus (moderate rectal inflation) and a psychological stimulus (anticipation of a visceral stimulus).
Results: In response to the visceral stimulus, women showed greater activation in the ventromedial prefrontal cortex, right anterior cingulate cortex, and left amygdala, whereas men showed greater activation of the right dorsolateral prefrontal cortex, insula, and dorsal pons/periaqueductal gray. Similar differences were observed during the anticipation condition. Men also reported higher arousal and lower fatigue.
Conclusions: Male and female patients with IBS differ in activation of brain networks concerned with cognitive, autonomic, and antinociceptive responses to delivered and anticipated aversive visceral stimuli.
Functional Brain Imaging in Irritable Bowel Syndrome With Rectal Balloon-Distention by Using fMRI
Yuan YZ, Tao RJ, Xu B, et al
World J Gastroenterol. 2003;9:1356-1360
Aim: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity is a key factor in the pathophysiology of IBS. The aim of this study was to examine the effect of rectal balloon-distention stimulus by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the distribution, extent, and intensity of activated areas between IBS patients and normal controls.
Methods: Twenty-six patients with IBS and eleven normal controls were tested for rectal sensation, and the subjective pain intensity at 90 ml and 120 ml rectal balloon-distention was reported by using Visual Analogue Scale. Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon-distention in all subjects.
Results: Rectal distention stimulation increased the activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon-distention, the activation area and percentage change in MR signal intensity of the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in patients with IBS than that in controls. Score of pain sensation at 90 ml and 120 ml rectal balloon-distention was significantly higher in patients with IBS than that in controls.
Conclusion: Using fMRI, some patients with IBS can be detected having visceral hypersensitivity in response to painful rectal balloon-distention. fMRI is an objective brain imaging technique to measure the change in regional cerebral activation more precisely. In this study, IC and PFC of the IBS patients were the major loci of the CNS processing of visceral perception.
Role of Visceral Sensitivity in the Pathophysiology of Irritable Bowel Syndrome
Delvaux M
Gut. 2002;51(suppl 1):i67-i71
Visceral hypersensitivity has been recognised as a characteristic of patients with irritable bowel syndrome (IBS). It may be involved in the pathogenesis of abdominal pain/discomfort, and seems to result from the sensitisation of nerve afferent pathways originating from the gastrointestinal tract. From a clinical point of view, hypersensitivity, although frequent, is not a constant finding among patients with IBS and cannot therefore be considered as a diagnostic marker of the condition. The advances made in understanding visceral hypersensitivity in patients with IBS are reviewed: the factors that influence abdominal distension are defined and different therapeutic perspectives are examined.
www.medscape.com/viewarti...02/7001/-1
Serotonin is released from the gut cells and that intiates the Peristaltic Reflex or contractions of the colon.
It is also used to signal pain from the gut to the brain.
Its also involved in appetite, pain, sex, anxiety, depression and most importantly how the gut works.
Another system is closely tied to the serotonin system and that is the HPA axis, which is the limbic system.
http://ibs.med.ucla.edu/Articles/PatientArticleSp97Breakthroughs.htm
The Hpa axis is also involved in the fight or flight system and in fighting infections.
Its in part the fight or flight system that acts as a trigger to symptoms. The antisipatory anxiety actives the fight or flight, which in turn releases histamine other stress hormones and chemicals which in turn cause the IBS to act up.
Gut Feelings: The Mind-Body Connection
http://www.ahealthyme.com/topic/mindbodygut;$sessionid$TJVAS2IAAETVTWCYSYZSFEQ
We are getting ahead of ourselves here somewhat though.
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My website on IBS is www.ibshealth.com
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