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All Boards >> Irritable Bowel Syndrome Research Library


Reged: 12/09/02
Posts: 7677
Loc: Seattle, WA
IBS: Improving Diagnosis, Serotonin Signaling, and Implications for Treatment
      07/05/05 03:30 PM

Authors: Lucinda Harris, MD; Lin Chang, MD

Over the past 50 years, evolving conceptual mechanisms have been proposed to explain the pathophysiology of IBS. These mechanisms have ranged from a purely psychological disorder to such physiologic conditions as a primary abnormality in gastrointestinal (GI) motility or visceral hypersensitivity. However, recent scientific data have increasingly supported that a dysregulation in brain-gut interactions resulting in alterations in GI motility, secretion, and sensation is the principal pathophysiologic mechanism underlying IBS.[1] Brain-gut interactions are mediated largely by the autonomic nervous system, which is comprised of the parasympathetic (vagal and sacral parasympathetic), sympathetic, and enteric nervous systems (ENS). Many factors (both central and peripheral) may contribute to an altered brain-gut axis, including genetic predisposition, chronic stress, inflammation/infection, and environmental parameters.[1] These alterations may subsequently lead to disturbances in intestinal motility, visceral sensitivity, and mucosal immune response and permeability. In IBS, these disturbances result in symptoms of abdominal pain or discomfort and altered bowel function, the defining characteristics of this disorder.[2]

There are many neurotransmitters and hormones that mediate bidirectional brain-gut communication. Serotonin (5-hydroxytryptamine [5-HT]) is one of the key mediators of gut motility, secretion, and sensation. Most of the serotonin is localized in the GI tract and is found in enterochromaffin (EC) cells and enteric neurons.[3] EC cells sense luminal factors such as food or mechanical distension in the gut, and release serotonin; 5-HT receptors on intrinsic primary afferent neurons (IPANs) as well as extrinsic spinal or vagal afferent neurons are activated. The ENS regulates secretion and peristalsis, whereas vagal and spinal afferents modulate nonpainful and painful sensations, respectively.[4] There are at least 7 main classes of 5-HT receptors. Particularly important for lower gut function and regulation are the 5-HT1P, 5-HT3, and 5-HT4 receptors. These receptors have been the focus of research evaluating the pathophysiologic mechanisms of IBS as well as targets for the development of novel agents in the treatment of functional gastrointestinal disorders. There is also evidence to suggest that other older serotonergic agents -- that is, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) -- may modulate intestinal function as well.[3] The roles of other neuropeptides and their receptors are also currently being explored as potential molecular targets for drug development.

The development of more effective treatment for IBS is crucial because it is one of the most common disorders seen by gastroenterologists and primary-care physicians, but patients are often not satisfied with traditional therapies. In addition, proper diagnosis and treatment are particularly critical for a number of reasons. Studies have demonstrated the dramatic impact of this disorder on the quality of life of patients with IBS compared with the general population and with individuals with other chronic health conditions.[5,6] In addition, patients with IBS utilize the healthcare system for both GI and non-GI complaints more than patients without IBS.[7] The latter in turn impacts the productivity of patients with IBS such that their absenteeism from work or school has been found to be 3 times higher than that of patients without IBS.[8] Not surprisingly, economic studies have demonstrated that this disorder is costly to the healthcare system and to the economic system as a whole, resulting in an annual associated cost of up to $30 billion.[9,10]

The challenge for clinicians is to identify individuals with IBS despite the fact that no diagnostic biologic marker currently exists for this disorder, and to manage their symptoms despite the lack of effective treatment. Studies evaluating the utility of symptom-based criteria and medical tests in the diagnosis of IBS vs organic GI disorders have resulted in recent recommendations for a more cost-effective diagnostic approach.[11] Although many patients may respond to reassurance, life-style changes, and traditional therapies, it is important for healthcare providers to familiarize themselves with advances in the pathophysiologic mechanisms of IBS that have subsequently led to the development of novel therapeutic agents, such as the serotonergic medications. In addition, these advances have inspired a new look at older medications that affect the serotonin receptors.

Copyright © 2003 Medscape.

Heather is the Administrator of the IBS Message Boards. She’s the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

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