Specialized Pro-resolving Mediators Reduce Pro-nociceptive Inflammatory Mediator Production in Models of Localized Provoked Vulvodynia.
Specialized Pro-resolving Mediators Reduce Pro-nociceptive Inflammatory Mediator Production in Models of Localized Provoked Vulvodynia.
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DOI：
10.1016/j.jpain.2021.03.144
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Foster DC
中科院分区：
文献类型：
--
作者：
Falsetta ML;Wood RW;Linder MA;Bonham AD;Honn KV;Maddipati KR;Phipps RP;Haidaris CG;Foster DC
局限性外阴疼痛(LPV)是绝经前妇女慢性性交困难的最常见原因，其特征是阴道开口周围的外阴前庭有轻微的疼痛。LPV的破坏性影响包括性功能障碍、不孕不育、抑郁，甚至自杀。然而，其病因尚不清楚。目前还没有有效的药物治疗方法；手术切除疼痛的前庭是最后的手段。在LPV中，前庭表现出独特的炎症特征，并伴随着促伤害性促炎介质前列腺素E2(PGE2)和白细胞介素6(IL-6)水平的升高，这与较低的机械敏感性阈值有关。专门的促分解介质(SPM)是体内内源性产生的脂类，通过在不损害宿主防御的情况下化解炎症，有望成为LPV的治疗方法。在13个市售的SPM中，有10个减少了外阴成纤维细胞在炎症刺激之前或之后的IL-6和PGE2的产生。使用小鼠外阴疼痛模型，将促炎介质定量与机械敏感性阈值测定相结合，局部应用SPM、MAX1、降低敏感性并抑制PGE2水平。二十二碳六烯酸(DHA)也能有效地降低外阴成纤维细胞中的PGE2，并迅速恢复小鼠的敏感阈值。总之，SPM及其前体可能是一种安全有效的治疗LPV的药物。
Localized provoked vulvodynia (LPV) is the most common cause of chronic dyspareunia in premenopausal women, characterized by pain with light touch to the vulvar vestibule surrounding the vaginal opening. The devastating impact of LPV includes sexual dysfunction, infertility, depression, and even suicide. Yet, its etiology is unclear. No effective medical therapy exists; surgical removal of the painful vestibule is the last resort. In LPV, the vestibule expresses a unique inflammatory profile with elevated levels of pro-nociceptive proinflammatory mediators prostaglandin E2 (PGE2) and interleukin-6 (IL-6), which are linked to lower mechanical sensitivity thresholds. Specialized pro-resolving mediators (SPMs), lipids produced endogenously within the body, hold promise as an LPV treatment by resolving inflammation without impairing host defense. Ten of 13 commercially available SPMs reduced IL-6 and PGE2 production by vulvar fibroblasts, administered either before or after inflammatory stimulation. Using a murine vulvar pain model, coupling proinflammatory mediator quantification with mechanical sensitivity threshold determination, topical treatment with the SPM, maresin 1, decreased sensitivity and suppressed PGE2 levels. Docosahexaenoic acid (DHA), a precursor of maresin 1, was also effective in reducing PGE2 in vulvar fibroblasts and rapidly restored mouse sensitivity thresholds. Overall, SPMs and their precursors may be a safe and efficacious for LPV.
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影响因子：
17.1
作者：
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