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在纤维肌痛的实验模型中,性别差异和雌二醇在痛觉过敏和感觉异常中的作用。

Sex differences and estradiol involvement in hyperalgesia and allodynia in an experimental model of fibromyalgia.

机构信息

Departamento de Farmacobiología, Cinvestav, Unidad Coapa, Calz. De los Tenorios 235, Col. Granjas Coapa, 14330 Mexico City, Mexico; Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo, Huipulco, 14370 Mexico City, Mexico.

Departamento de Farmacobiología, Cinvestav, Unidad Coapa, Calz. De los Tenorios 235, Col. Granjas Coapa, 14330 Mexico City, Mexico.

出版信息

Horm Behav. 2018 Jan;97:39-46. doi: 10.1016/j.yhbeh.2017.10.011. Epub 2017 Nov 8.

Abstract

Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome. Its prevalence in women is higher than in men possibly by hormonal factors given that symptoms are aggravated during sex hormone-related events, such as the premenstrual period, pregnancy, postpartum or menopause. The aim of the present study was to investigate whether hyperalgesia and allodynia, in reserpine-induced experimental FM, depend on sex, estrous cycle, ovariectomy and replacement with 17β-estradiol. To fulfill this objective, we compared males, intact females with known estrous cycle phases and ovariectomized (OVX) rats treated with 17β-estradiol. Data demonstrated that reserpine administration disrupted the normal estrous cycle and produced that all females entered metestrus/diestrus. In addition, this treatment leads to muscle hyperalgesia and tactile allodynia in a similar manner in male and intact female rats. However, the absence of ovarian hormones (in OVX rats) increased muscle nociception. 17β-estradiol (2.5-10μg/rat) produced antihyperalgesic and antiallodynic effects 24h, but not 8h, after its administration, suggesting a genomic mechanism. The present results support the validity of the reserpine-induced FM model for searching alternatives of treatment, particularly during endocrine phases when pain is exacerbated such as menopause, and that 17β-estradiol replacement might be useful.

摘要

纤维肌痛(FM)是一种肌肉骨骼慢性疼痛综合征。女性的患病率高于男性,可能与激素因素有关,因为症状在与性激素相关的事件(如月经前期、怀孕、产后或更年期)期间加重。本研究旨在探讨在利血平诱导的实验性 FM 中,痛觉过敏和感觉异常是否取决于性别、发情周期、卵巢切除术和用 17β-雌二醇替代。为了实现这一目标,我们比较了雄性、具有已知发情周期阶段的完整雌性和用 17β-雌二醇治疗的卵巢切除术(OVX)大鼠。数据表明,利血平给药破坏了正常的发情周期,导致所有雌性动物进入动情前期/动情后期。此外,这种治疗以类似的方式导致雄性和完整雌性大鼠的肌肉痛觉过敏和触觉感觉异常。然而,卵巢激素的缺失(在 OVX 大鼠中)增加了肌肉伤害感受。17β-雌二醇(2.5-10μg/大鼠)在给药后 24 小时而非 8 小时产生抗痛觉过敏和抗感觉异常作用,表明存在基因组机制。本研究结果支持利血平诱导的 FM 模型用于寻找治疗替代方案的有效性,特别是在疼痛加剧的内分泌阶段,如更年期,并且 17β-雌二醇替代可能有用。

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