Abstract
Visceral pain is the hallmark feature of irritable bowel syndrome (IBS), a gastrointestinal
disorder, which is more commonly diagnosed in women. Female IBS patients frequently
report a history of early life adversity (ELA); however, sex differences in ELA-induced
visceral pain and the role of ovarian hormones have yet to be investigated. Therefore,
we tested the hypothesis that ELA induces visceral hypersensitivity through a sexually
dimorphic mechanism mediated via estradiol. As a model of ELA, neonatal rats were
exposed to different pairings of an odor and shock to control for trauma predictability.
In adulthood, visceral sensitivity was assessed via a visceromotor response to colorectal
distension. Following ovariectomy and estradiol replacement in a separate group of
rats, the visceral sensitivity was quantified. We found that females that received
unpredictable odor-shock developed visceral hypersensitivity in adulthood. In contrast,
visceral sensitivity was not significantly different following ELA in adult males.
Ovariectomy reversed visceral hypersensitivity following unpredictable ELA, whereas
estradiol replacement reestablished visceral hypersensitivity in the unpredictable
group. This study is the first to show sex-related differences in visceral sensitivity
following unpredictable ELA. Our data highlight the activational effect of estradiol
as a pivotal mechanism in maintaining visceral hypersensitivity.
Perspective
This article directly implicates a critical role for ovarian hormones in maintaining
visceral hypersensitivity following ELA, specifically identifying the activational
effect of estradiol as a key modulator of visceral sensitivity. These data suggest
that ELA induces persistent functional abdominal pain in female IBS patients through
an estrogen-dependent mechanism.
Key words
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Article info
Publication history
Published online: January 23, 2013
Accepted:
November 15,
2012
Received in revised form:
November 6,
2012
Received:
August 23,
2012
Footnotes
Supported by a VA Merit Grant to B.G.-V.M. and a VA Rehabilitation Research Pre-Doctoral Fellowship to A.C.
The authors declare no conflict of interest.
Identification
Copyright
© 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.
