Deriving Novel Biomarkers of Localized Provoked Vulvodynia through Metabolomics: A Biological System Based Approach

项目总结 外阴疼痛是一种慢性疼痛障碍，影响高达15%的女性，并导致严重的 与健康相关的生活质量。激惹前庭痛(PVD)，一种局限性激发性外阴疼痛(以前 称为外阴前庭炎综合征)包括阴道穿透时的剧烈疼痛和 在没有检测到的情况下用棉签触摸外阴前庭时的外阴灼痛 感染性的、神经性的或免疫学的解释这种疾病的治疗因缺乏 关于潜在症状的生物学机制的知识。人类阴道微生物区系起着重要的作用 在预防一些泌尿生殖系统疾病方面发挥关键作用。浅谈蚀变的关联性 外阴疼痛患者的阴道微生物群组成稀少，但为 微生物区系的参与。发现微生物群与PVD之间的关联对 针对女童和妇女的个性化预防、实用、有针对性的诊断性检测和个性化治疗 患有PVD。研究表明，大脑区域参与处理/调制来自外部的信号 外阴疼痛受试者的生殖器发生改变，这些改变与疼痛的主观报告有关 和阴道肌肉压痛。越来越多的临床前和新兴临床证据表明，微生物区系 它们的代谢产物可能在大脑活动和中枢信号的调节中发挥重要作用 系统，以及在疼痛和精神障碍的病因学和病理生理学中的潜在作用。在 目前的建议是，我们将评估50名女性的阴道微生物区系以及血浆和阴道代谢物 健康对照组和50例PVD受试者。PVD科目也将在我们广泛的 表型研究(Labus/Rapkin R01 HD076756)，我们使用脑成像来评估结构和 大脑功能以及临床、遗传、生理和生物参数。这项研究将测试 1)微生物区系组成和/或代谢物特征区分PVD患者和HCS的假设 以及在PVD受试者中，2)微生物区系组成和/或代谢物特征与PVD相关 症状严重程度、压痛敏感性、感受到的压力和创伤病史，以及3)微生物区系 成分和/或代谢物特征与PVD脑区改变相关，提示可能存在 微生物区系与大脑结构/功能之间的相互作用。

PROJECT SUMMARY Vulvodynia is a chronic pain disorder affecting up to 15% of women and resulting in substantial impairment in health related quality of life. Provoked Vestibulodynia (PVD), a form of localized provoked vulvodynia (formerly called vulvar vestibulitis syndrome) consists of severe pain upon vaginal penetration and objective findings of vulvar burning pain when touching the vulvar vestibule with a cotton swab in the absence of detectable infectious, neurological or immunological explanation The treatment of the disorder is hampered by a lack of knowledge regarding the biological mechanism underlying symptoms. The human vaginal microbiota play a key role in preventing a number of urogenital diseases. Research on the association between altered composition of the vaginal microbiome in vulvodynia is sparse, but provides tentative support for the involvement of microbiota. Discovering an association between microbiome and PVD has great implications for personalized prevention, practical, targeted diagnostic testing, and personalized therapy for girls and women with PVD. Research indicates brain regions involved in the processing/modulation of signals from the external genitals are altered in vulvodynia subjects and that these alterations correlate with subjective reports of pain and vaginal muscle tenderness. There is growing preclinical and emerging clinical evidence that the microbiota and their metabolites may play a significant role in the modulation of brain activity and central signaling systems, and a potential role in the etiology and pathophysiology of pain and psychiatric disorders. In the current proposal, we will assess the vaginal microbiota and plasma and vaginal metabolites of 50 female healthy controls and 50 PVD subjects. The PVD subjects will have also been enrolled in our extensive phenotyping study (Labus/Rapkin R01 HD076756) where we use brain imaging to assess the structure and function of the brain along with clinical, genetic, physiological, and biological parameters. This study will test the hypotheses that 1) Microbiota composition and/or metabolite profiles discriminate PVD patients from HCs as well as within PVD subjects, 2) Microbiota composition and/or metabolite profiles are correlated with PVD symptom severity, pressure pain sensitivity, perceived stress and trauma history, and 3) Microbiota composition and/or metabolite profiles are correlated with brain regions altered in PVD, suggesting a possible interaction between the microbiota and the brain structure/function.