VA Medical Center, Oklahoma City, Oklahoma 73104, USA.
J Pain. 2013 Mar;14(3):270-80. doi: 10.1016/j.jpain.2012.11.008. Epub 2013 Jan 21.
UNLABELLED: 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.
未标记:内脏疼痛是肠易激综合征(IBS)的主要特征,这是一种胃肠道疾病,在女性中更为常见。女性 IBS 患者常报告有早期生活逆境(ELA)的病史;然而,ELA 引起的内脏疼痛的性别差异和卵巢激素的作用尚未得到研究。因此,我们假设 ELA 通过雌激素介导的性别二态机制引起内脏敏感性。作为 ELA 的模型,新生大鼠接受不同的气味和电击配对以控制创伤的可预测性。在成年期,通过结直肠扩张的内脏运动反应评估内脏敏感性。在另一组大鼠进行卵巢切除术和雌二醇替代后,量化了内脏敏感性。我们发现,接受不可预测的气味-电击的雌性在成年后会出现内脏敏感性增加。相比之下,ELA 后成年雄性的内脏敏感性没有显著差异。卵巢切除术逆转了不可预测的 ELA 后的内脏敏感性,而雌二醇替代在不可预测组中重新建立了内脏敏感性。这项研究首次表明,不可预测的 ELA 后内脏敏感性存在性别差异。我们的数据强调了雌激素的激活作用作为维持内脏敏感性的关键机制。
观点:本文直接表明卵巢激素在维持 ELA 后内脏敏感性方面起着关键作用,特别是确定了雌激素的激活作用是内脏敏感性的关键调节剂。这些数据表明,ELA 通过雌激素依赖性机制在女性 IBS 患者中引起持续性功能性腹痛。
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