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

通过代谢组学推导局部诱发性外阴痛的新生物标志物：基于生物系统的方法

基本信息

批准号：
9322201
负责人：
JENNIFER S LABUS
金额：
$ 23.1万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9322201
关键词：
Adult Affect Afferent Pathways Behavioral Biological Biological Markers Blood Circulation Brain Brain imaging Brain region Burning Pain Characteristics Chemicals Chronic Chronic disabling pain Clinical Data Diagnostic tests Disease Enrollment Etiology Female Functional disorder Genital system Gossypium Hormonal Human Immunologics Impairment Infection Knowledge Lactobacillus Lead Life Mass Spectrum Analysis Medical Genetics Mental disorders Muscle Neurobiology Neurologic Organism Pain Pain Disorder Pain Threshold Patients Penetration Peripheral Persistent pain Phenotype Physiological Plasma Play Production Public Health Recording of previous events Reporting Research Role Sample Size Sensory Sensory Nerve Endings Severities Signal Transduction Spinal Cord Stress Structure Subgroup Swab Symptoms Syndrome System Testing Touch sensation Trauma Urogenital Diseases Vagina Vestibule Vestibulodynia Visceral Vulva Vulvodynia Woman base biological systems central pain chronic pain dynamic system endophenotype girls gut microbiota health related quality of life illness length improved individualized prevention insight metabolomics microbial microbiome microbiota novel novel marker personalized medicine pre-clinical pressure prevent pyrosequencing response somatosensory vaginal microbiome vulvar vestibulitis

项目摘要

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.

项目总结