Dysregulation in Sphingolipid Signaling Pathways is Associated With Symptoms and Functional Connectivity of Pain Processing Brain Regions in Provoked Vestibulodynia.
Ceramides
functional connectivity strength
graph theory
metabolomics
pain
provoked vestibulodynia
resting-state brain connectivity
sphingolipid metabolism
vulvodynia
Journal
The journal of pain
ISSN: 1528-8447
Titre abrégé: J Pain
Pays: United States
ID NLM: 100898657
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
22
12
2020
revised:
27
03
2021
accepted:
29
04
2021
pubmed:
25
5
2021
medline:
1
3
2022
entrez:
24
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34029688
pii: S1526-5900(21)00231-5
doi: 10.1016/j.jpain.2021.04.017
pmc: PMC10460622
mid: NIHMS1913493
pii:
doi:
Substances chimiques
Biomarkers
0
Sphingolipids
0
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1586-1605Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK048351
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK089201
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD091731
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES029462
Pays : United States
Informations de copyright
Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.
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