Federici Lauren M, Roth Sarah Dorsey, Krier Connie, Fitz Stephanie D, Skaar Todd, Shekhar Anantha, Carpenter Janet S, Johnson Philip L
1Department of Anatomy and Cell Biology 2Program in Medical Neurosciences, Paul and Carole Stark Neurosciences Research Institute 3Department of Psychiatry 4Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 5Indiana University School of Nursing, Indianapolis, IN 6Indiana Clinical and Translational Sciences Institute, Indiana University School of Medicine, Indianapolis, IN.
Menopause. 2016 Nov;23(11):1257-1266. doi: 10.1097/GME.0000000000000699.
As longitudinal studies determined that anxiety is a strong risk factor for hot flashes, we hypothesized that an anxiogenic stimulus that signals air hunger (hypercapnic, normoxic gas) would trigger an exacerbated hot flash-associated increase in tail skin temperature (TST) in a rat ovariectomy (OVEX) model of surgical menopause and hot flashes in symptomatic postmenopausal women. We also assessed TST responses in OVEX serotonin transporter (SERT) rats that models a common polymorphism that is associated with increased climacteric symptoms in postmenopausal women and increases in anxiety traits.
OVEX and sham-OVEX rats (initial experiment) and wildtype and SERT OVEX rats (subsequent experiment) were exposed to a 5-minute infusion of 20% carbon dioxide (CO2) normoxic gas while measuring TST. Postmenopausal women were given brief 20% and 35% CO2 challenges, and hot flashes were self-reported and objectively verified.
Compared to controls, OVEX rats had exacerbated increases in TST, and SERT OVEX rats had prolonged TST increases following CO2. Most women reported mild/moderate hot flashes after CO2 challenges, and the hot flash severity to CO2 was positively correlated with daily hot flash frequency.
The studies demonstrate that this anxiogenic stimulus is capable of inducing cutaneous vasomotor responses in OVEX rats, and eliciting hot flashes in postmenopausal women. In rats, the severity of the response was mediated by loss of ovarian function and increased anxiety traits (SERT), and, in women, by daily hot flash frequency. These findings may provide insights into anxiety-related triggers and genetic risk factors for hot flashes in thermoneutral environments.
由于纵向研究确定焦虑是潮热的一个重要风险因素，我们推测，一种提示空气饥饿的致焦虑刺激（高碳酸、常氧气体）会在手术绝经和有症状的绝经后女性潮热的大鼠卵巢切除术（OVEX）模型中引发与潮热相关的尾部皮肤温度（TST）加剧升高。我们还评估了OVEX血清素转运体（SERT）大鼠的TST反应，该模型模拟了一种常见的多态性，与绝经后女性更年期症状增加和焦虑特质增加有关。
在测量TST的同时，将OVEX和假手术OVEX大鼠（初始实验）以及野生型和SERT OVEX大鼠（后续实验）暴露于5分钟的20%二氧化碳（CO2）常氧气体输注中。对绝经后女性进行短暂的20%和35% CO2激发试验，并让她们自我报告潮热情况并进行客观验证。
与对照组相比，OVEX大鼠的TST升高加剧，而SERT OVEX大鼠在接触CO2后TST升高持续时间更长。大多数女性在CO2激发试验后报告有轻度/中度潮热，且潮热对CO2的严重程度与每日潮热频率呈正相关。
这些研究表明，这种致焦虑刺激能够在OVEX大鼠中诱导皮肤血管舒缩反应，并在绝经后女性中引发潮热。在大鼠中，反应的严重程度由卵巢功能丧失和焦虑特质增加（SERT）介导，而在女性中，则由每日潮热频率介导。这些发现可能为热中性环境中与焦虑相关的潮热触发因素和遗传风险因素提供见解。
