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1 Department of Medicine, CNS: Center for Neurovisceral Sciences & Women's Health, Los Angeles, CA, USA; David Geffen School of Medicine at UCLA, VAGLAHS, CURE: Digestive Diseases Research Center, Los Angeles, CA, USA
2 Department of Medicine, CNS: Center for Neurovisceral Sciences & Women's Health, Los Angeles, CA, USA
3 Department of Psychiatry and Biobehavioral Sciences and Brain Research Institute, CNS: Center for Neurovisceral Sciences & Women's Health, Los Angeles, CA, USA
4 Division of Gastroenterology, Gastrointestinal Neuropeptide Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
5 Department of Medicine, CNS: Center for Neurovisceral Sciences & Women's Health, Los Angeles, CA, USA; Department of Physiology, CNS: Center for Neurovisceral Sciences & Women's Health, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences and Brain Research Institute, CNS: Center for Neurovisceral Sciences & Women's Health, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: emayer{at}ucla.edu.
Background & Aims: Chronic stress plays an important role in the development and
exacerbation of symptoms in functional gastrointestinal disorders. To better understand the
mechanisms underlying this relationship, we aimed to characterize changes in visceral and
somatic nociception, colonic motility, anxiety-related behavior and mucosal immune activation
in rats exposed to 10 days of chronic psychological stress. Methods: Male Wistar rats were
submitted daily to either 1-h water avoidance (WA) stress or sham WA for 10 consecutive days.
The visceromotor response to colorectal distension, thermal somatic nociception, and behavioral
responses to an open field test were measured at baseline and after chronic WA. Fecal pellets
were counted after each WA stress or sham WA session as a measure of stress-induced colonic
motility. Colonic samples were collected from both groups and evaluated for structural changes
and neutrophil infiltration, mast cell number by immunohistochemistry, and cytokine expression
by quantitative RT-PCR. Results: Rats exposed to chronic WA (but not sham stress) developed
persistent visceral hyperalgesia while only transient changes in somatic nociception were
observed. Chronically stressed rats also exhibited anxiety-like behaviors, enhanced fecal pellet
excretion, small, but significant increases in the mast cell numbers and the expression of IL-1
and IFN-
. Visceral hyperalgesia following chronic stress persisted for at least a month.
Conclusions: Chronic psychological stress in rats results in a robust and long-lasting alteration
of visceral, but not somatic nociception. Visceral hyperalgesia is associated with other behavioral
manifestations of stress sensitization but was only associated with minor colonic immune
activation arguing against a primary role of mucosal immune activation in the maintenance of
this phenomenon.
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