Glucocorticoid signaling mediates stress-induced migraine-like behaviors in a preclinical mouse model.

IF 5 2区 医学 Q1 CLINICAL NEUROLOGY
Ya-Yu Hu, Rimenez Souza, Athithyaa Muthuraman, Leela Knapp, Christa McIntyre, Gregory Dussor
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Abstract

Background: Stress is one of the most common precipitating factors in migraine and is identified as a trigger in nearly 70% of patients. Responses to stress include release of glucocorticoids as an adaptive mechanism, but this may also contribute to migraine attacks. Here, we investigated the role of glucocorticoids on stress-induced migraine-like behaviors.

Methods: We have shown previously that repeated stress in mice evokes migraine-like behavioral responses and priming to a nitric oxide donor. Metyrapone, mifepristone, and corticosterone (CORT) were used to investigate whether CORT contributes to the stress-induced effects. Facial mechanical hypersensitivity was evaluated by von Frey testing and grimace scoring assessed the presence of non-evoked pain. We also measured serum CORT levels in control, stress, and daily CORT injected groups of both male and female mice.

Results: Metyrapone blocked stress-induced responses and priming in male and female mice. However, repeated CORT injections in the absence of stress only led to migraine-like behaviors in females. Both female and male mice showed similar patterns of serum CORT in response to stress or exogenous administration. Finally, administration of mifepristone, the glucocorticoid receptor antagonist, prior to each stress session blocked stress-induced behavioral responses in male and female mice.

Conclusions: These findings demonstrate that while CORT synthesis and receptor activation is necessary for the behavioral responses triggered by repeated stress, it is only sufficient in females. Better understanding of how glucocorticoids contribute to migraine may lead to new therapeutic opportunities.

糖皮质激素信号在临床前小鼠模型中介导压力诱发的偏头痛样行为。
背景:压力是偏头痛最常见的诱发因素之一,近70%的偏头痛患者将压力视为诱因。对压力的反应包括释放糖皮质激素作为一种适应机制,但这也可能导致偏头痛发作。在此,我们研究了糖皮质激素对应激诱发的偏头痛样行为的作用:方法:我们之前已经证明,小鼠反复应激会诱发偏头痛样行为反应和一氧化氮供体引物。我们使用甲基屈他酮(Metyrapone)、米非司酮(mifepristone)和皮质酮(CORT)来研究 CORT 是否有助于应激诱导效应。通过 von Frey 测试评估面部机械过敏性,并通过面无表情评分评估是否存在非诱发性疼痛。我们还测量了对照组、应激组和每日注射 CORT 组雌雄小鼠的血清 CORT 水平:结果:米屈肼酮可阻断雌雄小鼠的应激反应和诱发反应。然而,在没有压力的情况下重复注射 CORT 只会导致雌性小鼠出现类似偏头痛的行为。雌性和雄性小鼠的血清 CORT 对应激或外源性给药的反应模式相似。最后,在每次应激前给予糖皮质激素受体拮抗剂米非司酮可阻止雌雄小鼠的应激诱导行为反应:这些研究结果表明,虽然CORT的合成和受体激活是反复应激引发行为反应的必要条件,但只有雌性小鼠才有足够的条件。更好地了解糖皮质激素如何导致偏头痛可能会带来新的治疗机会。
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来源期刊
Cephalalgia
Cephalalgia 医学-临床神经学
CiteScore
10.10
自引率
6.10%
发文量
108
审稿时长
4-8 weeks
期刊介绍: Cephalalgia contains original peer reviewed papers on all aspects of headache. The journal provides an international forum for original research papers, review articles and short communications. Published monthly on behalf of the International Headache Society, Cephalalgia''s rapid review averages 5 ½ weeks from author submission to first decision.
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