Allodynia by Splenocytes From Mice With Acid-Induced Fibromyalgia-Like Generalized Pain and Its Sexual Dimorphic Regulation by Brain Microglia.

Allodynia by Splenocytes From Mice With Acid-Induced Fibromyalgia-Like Generalized Pain and Its Sexual Dimorphic Regulation by Brain Microglia.
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DOI:
10.3389/fnins.2020.600166
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发表时间:
2020
影响因子:
4.3
通讯作者:
Uchida H
Uchida H
中科院分区:
医学2区
文献类型:
--
作者:
Ueda H;Dozono N;Tanaka K;Kaneko S;Neyama H;Uchida H

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纤维肌痛(FM)是一种病因不明的疾病,以慢性全身性疼痛为特征,在腓肠肌反复注射酸性生理盐水诱导的动物模型中部分重现。在这里,我们试图在重复酸盐诱导的fm样广泛性疼痛(AcGP)模型中研究疼痛超敏反应(机械异常性痛和对电刺激的超敏反应)的性别差异。第0/D0天第一次单侧胃酸注射到腓肠肌,第5天第二次注射(第0天后,P0)分别引起雄性和雌性小鼠两侧短暂和持久的机械异常性疼痛。性腺切除术预处理对雄性和雌性小鼠第一次注射诱导的异常痛感没有影响,但在雄性小鼠中逐渐逆转第二次注射诱导的异常痛感,而雌性小鼠没有。此外,在D4-P4或P5-P11期间,脑室内二甲胺四环素可消除雄性小鼠的AcGP,但在D0-D5期间,雄性小鼠没有,而雌性小鼠没有,这表明AcGP需要脑小胶质细胞以晚发性和性别依赖的方式产生。我们还发现,静脉注射AcGP治疗的雄性小鼠而不是雌性小鼠的脾细胞会引起幼年小鼠的异位性疼痛。此外,从酸处理的雄性小鼠的脾细胞中提取的纯化CD4+ T细胞保留了在幼稚小鼠中引起异位性疼痛的能力。这些发现表明,fm样AcGP具有多种两性二态机制。
Fibromyalgia (FM), a disease of unknown etiology characterized by chronic generalized pain, is partly recapitulated in an animal model induced by repeated acid saline injections into the gastrocnemius muscle. Here, we attempted to investigate the sex difference in pain hypersensitivity (mechanical allodynia and hypersensitivity to electrical stimulation) in the repeated acid saline-induced FM-like generalized pain (AcGP) model. The first unilateral acid injection into gastrocnemius muscle at day 0/D0 and second injection at D5 (post day 0, P0) induced transient and long-lasting mechanical allodynia, respectively, on both sides of male and female mice. The pretreatment with gonadectomy did not affect the first injection-induced allodynia in both sexes, but gradually reversed the second injection-induced allodynia in male but not female mice. Moreover, the AcGP in male mice was abolished by intracerebroventricular minocycline treatments during D4–P4 or P5–P11, but not by early treatments during D0–D5 in male but not female mice, suggesting that brain microglia are required for AcGP in late-onset and sex-dependent manners. We also found that the intravenous treatments of splenocytes derived from male but not female mice treated with AcGP caused allodynia in naive mice. In addition, the purified CD4+ T cells derived from splenocytes of acid-treated male mice retained the ability to cause allodynia in naive mice. These findings suggest that FM-like AcGP has multiple sexual dimorphic mechanisms.
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发表时间: 2019-01
期刊: Brain, behavior, and immunity
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发表时间: 2020-12
期刊: Pain
影响因子: 7.4
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DOI: 10.1111/j.1476-5381.1957.tb01354.x
发表时间: 1957-01-01
期刊: BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
影响因子: --
作者:
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