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In contrast to the
conscious perception of all sensory stimuli affecting our external body
surface, the great majority of events within the gastrointestinal tract
such as the chemical breakdown of food, the absorption of nutrients or
the involuntary peristaltic action of the gut are not consciously perceived
in the healthy state. However, an alteration in perception of sensations
arising from the gut has been implicated in the generation of symptoms
in patients with Irritable Bowel Syndrome (IBS). Even though studies investigating
gastrointestinal sensitivity date back to the early 1900’s and reports
describing sensory disturbances of the gut in patients with IBS first
appeared in the 1970’s, it is not until recently that well-controlled
studies using controlled experimental distension of the gut have begun
to characterize the mechanisms underlying IBS symptom generation. The
most commonly reported perceptual abnormality in IBS patients has been
a lowered discomfort threshold to rectosigmoid balloon distension. However,
only a subset of IBS patients shows this perceptual alteration during
baseline conditions and recent evidence suggests that the abnormality
is more related to hypervigilance rather than increased pain perception.
In a recent study
published in Gastroenterology, investigators from the UCLA Neuroenteric
Disease Section tested the hypothesis that IBS patients show an altered
perceptual response to irritation of the gastrointestinal tract by repetitive
distension. They found that even though IBS patients may have normal pain
thresholds during rectal balloon distension under control conditions,
repetitive colonic distension results in an enhanced perception of intestinal
stimuli in nearly 100% of IBS patients. In contrast, in healthy control
subjects, no such sensitization was observed, while some patients with
inflammatory bowel disease even developed intestinal hyposensitivity.
The findings by the
UCLA researchers are consistent with several clinical observations that
suggest a compromised ability of IBS patients to activate the body’s own
pain inhibition systems in response to irritation of the digestive tract.
For example, the fact that healthy subjects do not perceive even the most
intense sigmoid contractions during stress and following food intake,
in IBS patients such prolonged high intensity sigmoid motor activity may
result in sensitization of the colon, manifesting as pain and discomfort.
Similarly, the fact that certain individuals with documented enteric infections
and associated colonic inflammation will develop a prolonged IBS-like
syndrome, while the majority of people will become asymptomatic once the
infection is cleared, is consistent with a model by which a compromised
ability of the nervous system to counter regulate sensitization of sensory
nerve pathways during inflammation. Several studies are underway at UCLA
to identify the cause for this abnormality, and to identify the regions
and receptors within the nervous system that could be involved.
These findings not
only have significant implications for our understanding of mechanisms
underlying IBS symptom generation, but they also form the basis for a
series of new studies testing the efficacy of several promising new drug
therapies for IBS. Without having to evaluate symptom responses in hundreds
of patients, the colorectal sensitization study makes it possible to determine
quickly if a newly developed IBS drug can prevent the development of sensitization.
Should you be interested
in more information about these exciting research studies, or should you
consider to participate, please call at (310) 268-3432.
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