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

项目摘要 外阴疼痛是一种慢性疼痛疾病，影响高达15%的女性，并导致严重损害， 健康相关的生活质量。诱发性前庭痛（PVD），一种局部诱发性外阴痛（以前称为外阴痛）， 称为外阴前庭炎综合征）包括阴道插入时的剧烈疼痛和 外阴灼热疼痛时触摸外阴前庭用棉签在没有检测到 感染性、神经学或免疫学的解释。 关于潜在症状的生物学机制的知识。人类阴道微生物群发挥着 在预防一些泌尿生殖系统疾病中起关键作用。改变的关联性研究 外阴痛的阴道微生物组的组成是稀疏的，但提供了初步的支持， 微生物群的参与。发现微生物组与PVD之间的关联对以下方面具有重大意义： 为女孩和妇女提供个性化预防、实用、有针对性的诊断检测和个性化治疗 PVD的。研究表明，大脑区域参与处理/调制来自外部的信号， 外阴痛受试者的生殖器发生改变，这些改变与疼痛的主观报告相关， 和阴道肌肉压痛越来越多的临床前和临床证据表明， 其代谢产物可能在脑活动和中枢信号传导的调节中起重要作用 系统，并在疼痛和精神疾病的病因学和病理生理学的潜在作用。在 根据目前的提议，我们将评估50名女性的阴道微生物群、血浆和阴道代谢物。 健康对照组和50名PVD受试者。PVD受试者也将参加我们广泛的 表型研究（Labus/Rapkin R 01 HD 076756），其中我们使用脑成像来评估结构， 大脑的功能沿着临床、遗传、生理和生物学参数。这项研究将测试 假设1）微生物群组成和/或代谢物谱将PVD患者与HC区分开来 2）微生物群组成和/或代谢物谱与PVD相关 症状严重程度、压力疼痛敏感性、感知压力和创伤史，以及3）微生物群 组成和/或代谢产物谱与PVD中改变的脑区域相关，这表明可能的 微生物群与大脑结构/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.