Irritable Bowel Syndrome Message Boards | Re: UVM Researchers Identify Molecular Changes in IBS Patients- ShawnEric, plz provide links-

Hi,
I really appreciate all the items you post for us but I also like to read the original articles myself. Unfortunately, the post I've copied below that you wrote to Shanna on 11/16 doesn't have any links to the numerous articles you first listed- [see copy of your post below]- and then the first link that you did give in your original post doesn't work as of today.

Would you plz re-post these articles w/ links to all of the original full article and also, hopefully you can find the correct link to replace the one that not's working now.

Lastly, have you read anywhere about the use of Zelnorm and one of the SSRI's in the same patient? I know Z is very new but I'm curious if it's been evaluated yet in C-IBS patients who are also taking an SSRI? The goal of using an SSRI is to increase the serotonin levels in the brain and of Z to increase the serotonin activity in the gut, altho via different cellular mechanisms and at diff receptor sites. So it seems to me that it'd be OK for a C-IBS patient to take both, if using an SSRI is indicated and the Z is already working to help the patient. What do you think?

Thanks for all your help, both now and all over this excellent board!

LL

Copy of your post to Shanna: [11/16/03]
Shana, I understand what your saying however this doesn't have to do with the drugs, it is confirmed in other avenues and there is a huge body of research on it.

Also there are reasons why that drug might not have worked for you personally.

The two systems in major research that seem to be important in IBS research right now are the serotonin system and the HPA axis.

For example on serotonin and IBS,

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;3suppl 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;3suppl 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-11CMethyl-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-11Cmethyl-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

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Many years of C-IBS and pain too for past 2 years-

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