Repeated Vulvovaginal Fungal Infections Cause Persistent Pain in a Mouse Model of Vulvodynia
Repeated Vulvovaginal Fungal Infections Cause Persistent Pain in a Mouse Model of Vulvodynia
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DOI：
10.1126/scitranslmed.3002613
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发表时间：
2011-09-21
影响因子：
17.1
通讯作者：
Mogil, Jeffrey S.
中科院分区：
文献类型：
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作者：
Farmer, Melissa A.;Taylor, Anna M.;Mogil, Jeffrey S.
诱发性前庭痛是外阴痛（不明原因的外阴疼痛）的最常见形式，是一种常见的特发性疼痛疾病，与复发性念珠菌病（酵母菌感染）病史相关。其特征是外阴异常性疼痛（对触摸的疼痛性过敏）和神经支配过度。我们测试了外阴反复局部接触常见真菌病原体是否会导致慢性疼痛的发生。一部分遭受反复白色念珠菌感染的雌性小鼠出现了局限于外阴的机械性异常性疼痛。患有异常性疼痛的小鼠还表现出肽能伤害感受器和交感纤维的过度神经支配（如阴道上皮中蛋白质基因产物 9.5、降钙素基因相关肽和囊泡单胺转运蛋白 2 免疫反应性增加所示）。在单次、长期念珠菌感染后，以及用酵母聚糖（一种真菌抗原的混合物）诱导反复外阴（但不是后爪）炎症后，也观察到部分小鼠出现持久的行为异常性疼痛。超敏反应和过度神经支配均在感染和炎症消退后至少 3 周出现。我们的数据表明，感染在消退后很长时间内仍可引起持续性疼痛，并且复发性酵母菌感染在小鼠中复制了人类引起的外阴痛的重要特征。
Provoked vestibulodynia, the most common form of vulvodynia (unexplained pain of the vulva), is a prevalent, idiopathic pain disorder associated with a history of recurrent candidiasis (yeast infections). It is characterized by vulvar allodynia (painful hypersensitivity to touch) and hyperinnervation. We tested whether repeated, localized exposure of the vulva to a common fungal pathogen can lead to the development of chronic pain. A subset of female mice subjected to recurrent Candida albicans infection developed mechanical allodynia localized to the vulva. The mice with allodynia also exhibited hyperinnervation with peptidergic nociceptor and sympathetic fibers (as indicated by increased protein gene product 9.5, calcitonin gene-related peptide, and vesicular monoamine transporter 2 immunoreactivity in the vaginal epithelium). Long-lasting behavioral allodynia in a subset of mice was also observed after a single, extended Candida infection, as well as after repeated vulvar (but not hind paw) inflammation induced with zymosan, a mixture of fungal antigens. The hypersensitivity and hyperinnervation were both present at least 3 weeks after the resolution of infection and inflammation. Our data show that infection can cause persistent pain long after its resolution and that recurrent yeast infection replicates important features of human provoked vulvodynia in the mouse.