Sexually Dimorphic Effects of Unpredictable Early Life Adversity on Visceral Pain Behavior in a Rodent Model
Sexually Dimorphic Effects of Unpredictable Early Life Adversity on Visceral Pain Behavior in a Rodent Model
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DOI：
10.1016/j.jpain.2012.11.008
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发表时间：
2013-03-01
期刊：
影响因子：
4
通讯作者：
Greenwood-Van Meerveld, Beverley
中科院分区：
文献类型：
--
作者：
Chaloner, Aaron;Greenwood-Van Meerveld, Beverley
内脏疼痛是肠易激综合征（IBS）的标志性特征，肠易激综合征是一种胃肠道疾病，在女性中更常见。女性IBS患者经常报告早期生活逆境（ELA）的历史;然而，ELA引起的内脏疼痛的性别差异和卵巢激素的作用还有待研究。因此，我们检验了ELA通过雌二醇介导的性二态性机制诱导内脏高敏感性的假设。作为ELA的模型，新生大鼠暴露于不同配对的气味和休克，以控制创伤的可预测性。在成年期，通过内脏对结直肠扩张的反应来评估内脏敏感性。在另一组大鼠中进行卵巢切除术和雌二醇替代后，定量内脏敏感性。我们发现，女性接受不可预测的气味休克发展内脏高敏感性在成年期。与此相反，内脏的敏感性没有显着不同ELA在成年男性。卵巢切除术逆转内脏高敏感性不可预测的ELA，而雌二醇替代重建内脏高敏感性不可预测的组。这项研究是第一个显示在不可预测的ELA后内脏敏感性的性别相关差异。我们的数据突出雌二醇的激活作用作为一个关键的机制，在维持内脏hypersensitive.Perspective：本文直接牵连卵巢激素在维持内脏高敏感性ELA后的关键作用，特别是确定作为内脏敏感性的关键调制器雌二醇的激活作用。这些数据表明，ELA通过雌激素依赖性机制诱导女性IBS患者持续性功能性腹痛。(C)2013年，美国疼痛协会。爱思唯尔公司出版版权所有
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. (C) 2013 by the American Pain Society. Published by Elsevier Inc. All rights reserved