A cautionary tale: Non-steroidal anti-inflammatory drug use and localized provoked vulvodynia

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Pain Pub Date : 2025-09-11 DOI:10.1016/j.jpain.2025.105559

Emanuelle Chrysilla , Sarah Fischer , Ji-Mi Jang , Krishna Rao Maddipati , Tanzy M.T. Love , Mitchell A. Linder , Megan L. Falsetta

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引用次数: 0

Abstract

Localized provoked vulvodynia (LPV) is characterized by chronic vulvar pain upon light touch to the vulvar vestibule, a specialized ring of tissue immediately surrounding the vaginal opening. LPV affects ∼14 million people in the US. Current treatments for LPV include nonsteroidal anti-inflammatory drugs (NSAIDs), but clinical evidence has demonstrated that they are ineffective for vulvar pain. Here, the effects of NSAID treatment on inflammation and resolution in an in vitro model of LPV were explored using enzyme-linked immunosorbent assays (ELISAs), calcium imaging, and metabololipidomics. Additionally, the effectiveness of NSAID treatment on mitigating chronic vulvar pain was assessed using a validated LPV mouse model that mimics key features of vulvodynia. These findings indicate that although NSAID treatment reduced pro-inflammatory eicosanoid production in vulvar fibroblasts, lipidomic analysis revealed that COX inhibition also downregulated levels of pro-resolving lipids, namely epoxyeicosatrienoic acids (EETs), lipoxins (LXs), and resolvin E-series (RvEs). In vivo, NSAID treatment did not restore vulvar pain thresholds back to baseline levels in mice. Overall, this study offers one possible explanation for previous reports of the ineffectiveness of NSAIDs on managing LPV-associated vulvar pain.

Perspective

Taking NSAIDs to manage chronic vulvar pain may downregulate levels of specialized pro-resolving lipid mediators, thereby resulting in prolonged pain and delayed inflammation resolution. This study provides one possible explanation for clinical reports of the ineffectiveness of NSAIDs in the mitigation of vulvodynia-associated pain.

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一个警世故事：非甾体抗炎药的使用和局部性外阴痛。

局部诱发性外阴痛（LPV）的特征是外阴前庭（一种直接围绕阴道口的特殊组织环）轻触引起的慢性外阴疼痛。LPV在美国影响了大约1400万人。目前治疗LPV的方法包括非甾体抗炎药（NSAIDs），但临床证据表明它们对外阴疼痛无效。本研究采用酶联免疫吸附试验（elisa）、钙显像和代谢脂质组学，探讨了非甾体抗炎药治疗对LPV体外模型炎症和消退的影响。此外，通过模拟外阴痛关键特征的LPV小鼠模型，评估了非甾体抗炎药治疗缓解慢性外阴疼痛的有效性。这些发现表明，尽管非甾体抗炎药治疗减少了外阴成纤维细胞中促炎类二十烷酸的产生，但脂质组学分析显示，COX抑制也下调了促炎类脂的水平，即环氧二碳三烯酸（EETs）、脂质（LXs）和促炎蛋白e系列（RvEs）。在体内，非甾体抗炎药治疗并没有使小鼠外阴疼痛阈值恢复到基线水平。总的来说，这项研究为以前关于非甾体抗炎药对lpv相关外阴疼痛无效的报道提供了一种可能的解释。观点：服用非甾体抗炎药来治疗慢性外阴疼痛可能会下调专门的促溶解脂质介质的水平，从而导致疼痛延长和炎症消退延迟。这项研究为非甾体抗炎药在缓解外阴痛相关疼痛方面无效的临床报道提供了一种可能的解释。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pain 医学-临床神经学

CiteScore

6.30

自引率

7.50%

发文量

441

审稿时长

42 days

期刊介绍： The Journal of Pain publishes original articles related to all aspects of pain, including clinical and basic research, patient care, education, and health policy. Articles selected for publication in the Journal are most commonly reports of original clinical research or reports of original basic research. In addition, invited critical reviews, including meta analyses of drugs for pain management, invited commentaries on reviews, and exceptional case studies are published in the Journal. The mission of the Journal is to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals to publish original research.