{
    "abstract": "Provoked vestibulodynia (PVD) is a chronic pain disorder characterized by local hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Despite decades of study, the lack of identified biomarkers has slowed the development of effective therapies. The primary aim of this study was to use metabolomics to identify novel biochemical mechanisms in vagina and blood underlying brain biomarkers and symptoms in PVD, thereby closing this knowledge gap. Using a cross-sectional case-control observational study design, untargeted and unbiased metabolomic profiling of vaginal fluid and plasma was performed in women with PVD compared to healthy controls. In women with PVD, we also obtained assessments of vulvar pain, vestibular and vaginal muscle tenderness, and 24-hour symptom intensity alongside resting-state brain functional connectivity of brain regions involved in pain processing and modulation. Compared to healthy controls, women with PVD demonstrated differences primarily in vaginal (but not plasma) concentrations of metabolites of the sphingolipid signaling pathways, suggesting localized effects in vagina and vulvar vestibule rather than systemic effects. Our findings reveal that dysregulation of sphingolipid metabolism in PVD is associated with increased vulvar pain and muscle tenderness, sexual dysfunction, and decreased functional connectivity strength in pain processing/modulatory brain regions. This data collectively suggests that alterations in sphingolipid signaling pathways are likely an important molecular biomarker in PVD that could lead to new targets for therapeutic intervention. PERSPECTIVE: This manuscript presents the results of a robust, unbiased molecular assessment of plasma and vaginal fluid samples in women with provoked vestibulodynia compared to healthy controls. The findings suggest that alterations in sphingolipid signaling pathways are associated with symptoms and brain biomarkers and may be an important molecular marker that could provide new targets for therapeutic intervention.",
    "authors": [
        {
            "affiliation": "G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California; Brain Research Institute UCLA, Gonda (Goldschmied) Neuroscience and Genetics Research Center, Los Angeles, California. Electronic address: jlabus@g.ucla.edu.",
            "firstname": "Jennifer S",
            "initials": "JS",
            "lastname": "Labus"
        },
        {
            "affiliation": "G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California.",
            "firstname": "Emeran A",
            "initials": "EA",
            "lastname": "Mayer"
        },
        {
            "affiliation": "G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California.",
            "firstname": "Kirsten",
            "initials": "K",
            "lastname": "Tillisch"
        },
        {
            "affiliation": "Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas; Department of Molecular and Human Genetics, Bioinformatics Research Laboratory, Baylor College of Medicine, Houston, Texas; Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas.",
            "firstname": "Kjersti M",
            "initials": "KM",
            "lastname": "Aagaard"
        },
        {
            "affiliation": "G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California.",
            "firstname": "Jean",
            "initials": "J",
            "lastname": "Stains"
        },
        {
            "affiliation": "Metabolon, Inc, Research Triangle Park, North Carolina.",
            "firstname": "Katarzyna",
            "initials": "K",
            "lastname": "Broniowska"
        },
        {
            "affiliation": "G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California.",
            "firstname": "Charlotte",
            "initials": "C",
            "lastname": "Van Remortel"
        },
        {
            "affiliation": "G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California.",
            "firstname": "Guistinna",
            "initials": "G",
            "lastname": "Tun"
        },
        {
            "affiliation": "G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California; Department of Obstetrics and Gynecology, David Geffen School of Medicine at the University of California, Los Angeles, California.",
            "firstname": "Andrea",
            "initials": "A",
            "lastname": "Rapkin"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.jpain.2021.04.017",
    "journal": "The journal of pain",
    "keywords": [
        "Ceramides",
        "functional connectivity strength",
        "graph theory",
        "metabolomics",
        "pain",
        "provoked vestibulodynia",
        "resting-state brain connectivity",
        "sphingolipid metabolism",
        "vulvodynia"
    ],
    "methods": null,
    "publication_date": "2021-05-25",
    "pubmed_id": "34029688\n11129362\n31501296\n30817440\n24239768\n22045572\n32623813\n31749298\n27008217\n21031003\n31068460\n26166255\n32708516\n31445522\n26497128\n16530430\n20547229\n30802544\n9015038\n17403416\n26415722\n11967493\n23887335\n26703189\n31427962\n29875641\n31220089\n28239631\n25735001\n29391213\n15542936\n23578957\n31726468\n18216770\n26900066\n29363062\n25871646\n32170133\n30898151\n32385738\n33070438\n24960545\n27853523\n18751920\n27586833\n31411365\n32344505\n28760971\n23563670\n32205761\n30080865\n31687167\n33139708\n22267119\n28932680\n33042712\n32717258\n26944461\n15836975\n32614515\n20504069\n10782451\n23318139\n18930351\n25551965\n31004261\n29703731\n33065770\n28780001\n23707510\n28626422\n22859507\n26921767\n29756665\n22971335\n26965202\n31434538\n30734917\n29852336",
    "results": null,
    "title": "Dysregulation in Sphingolipid Signaling Pathways is Associated With Symptoms and Functional Connectivity of Pain Processing Brain Regions in Provoked Vestibulodynia.",
    "xml": "<Element 'PubmedArticle' at 0x788501d6bec0>"
}