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新生期母婴分离和慢性不可预测应激对成年大鼠偏头痛样行为的影响。

The effects of neonatal maternal deprivation and chronic unpredictable stresses on migraine-like behaviors in adult rats.

机构信息

Endodontology Research Center, Kerman University of Medical Sciences, Kerman, Iran; Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Department of Oral Pathology, School of Dentistry, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Neurosci Lett. 2022 Feb 16;772:136444. doi: 10.1016/j.neulet.2022.136444. Epub 2022 Jan 8.

Abstract

BACKGROUND

Stress is known to cause migraine. This study investigates the effects of neonatal maternal deprivation (MD) and chronic unpredictable stress (CUS) on migraine in rats.

METHODS

Seventy rats were randomly divided into ten groups (five groups of each sex, and seven rats/group). The groups included: untreated intact, nitroglycerin (NTG) only, NTG + MD, NTG + CUS (10 weeks after birth), and NTG + MD + CUS. For the induction of MD, pups were separated from their mothers from postnatal day 2 to day 14. The CUS was conducted by daily exposure to different stressors for 2 weeks. For the induction of migraine after stress, NTG (5 mg/kg/IP) was administered every second day for 9 days. Afterward, NTG-related symptoms, including climbing behavior, facial rubbing, body grooming, freezing behavior, and head-scratching, were recorded for 90 min. Statistical differences between the groups were analyzed by one-way and two-way ANOVA followed by the Newman-Keuls test.

RESULTS

Migraine symptoms, including increased head-scratching, facial rubbing, and decreased climbing behavior, were more significant in females than in males. Head scratching and facial rubbing increased in stressed females, but not in males as compared to NTG-treated rats. Body grooming was significantly decreased in MD males compared to the NTG group. The effects of NTG in MD + CUS on the rats did not differ from those in the MD or CUS groups.

CONCLUSIONS

MD and CUS had a sex-related aggravating effect on the development of migraine, while the combination of MD and CUS had no additive migraine-aggravating effect.

摘要

背景

压力已知可导致偏头痛。本研究旨在探讨新生期母鼠剥夺(MD)和慢性不可预测应激(CUS)对大鼠偏头痛的影响。

方法

70 只大鼠随机分为 10 组(每组雌雄各 5 组,每组 7 只)。包括:未处理的完整组、硝酸甘油(NTG)组、NTG+MD 组、NTG+CUS(出生后第 10 周)组和 NTG+MD+CUS 组。为了诱导 MD,幼鼠从出生后第 2 天到第 14 天与母鼠分离。CUS 通过每天暴露于不同的应激源持续 2 周进行。应激后诱导偏头痛,NTG(5mg/kg/IP)每隔一天给药,共 9 天。之后,记录 NTG 相关症状,包括攀爬行为、面部摩擦、身体梳理、冻结行为和挠头,持续 90 分钟。采用单因素和双因素方差分析,随后采用 Newman-Keuls 检验对组间差异进行分析。

结果

与雄性相比,雌性偏头痛症状(包括挠头、面部摩擦增加,攀爬行为减少)更为显著。与 NTG 处理组相比,应激后的雌性大鼠挠头和面部摩擦增加,但雄性大鼠无此现象。与 NTG 组相比,MD 雄性大鼠的身体梳理明显减少。与 MD 或 CUS 组相比,NTG 在 MD+CUS 组对大鼠的影响没有差异。

结论

MD 和 CUS 对偏头痛的发展有性别相关的加重作用,而 MD 和 CUS 的联合作用对偏头痛无累加加重作用。

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