Inflammation, lipid dysregulation, and transient receptor potential cation channel subfamily V member 4 signaling perpetuate chronic vulvar pain.

Autor:	Bekauri T; OB/GYN Research Division, University of Rochester, Rochester, NY, United States., Fischer S; OB/GYN Research Division, University of Rochester, Rochester, NY, United States., Honn KV; Pathology Department, Wayne State University, Detroit, MI, United States.; Lipidomics Core Facility and Bioactive Lipids Research Program, Wayne State University, Detroit, MI, United States., Maddipati KR; Pathology Department, Wayne State University, Detroit, MI, United States.; Lipidomics Core Facility and Bioactive Lipids Research Program, Wayne State University, Detroit, MI, United States., Love T; Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, United States., Little C; OB/GYN Research Division, University of Rochester, Rochester, NY, United States., Wood RW; OB/GYN Research Division, University of Rochester, Rochester, NY, United States., Bonham AD; OB/GYN Department, Oregon Health Sciences University, Portland, OR, United States., Linder MA; OB/GYN Research Division, University of Rochester, Rochester, NY, United States., Yule DI; Pharmacology and Physiology Department, University of Rochester, Rochester, NY, United States., Emanuelle C; Pharmacology and Physiology Department, University of Rochester, Rochester, NY, United States., Falsetta ML; OB/GYN Research Division, University of Rochester, Rochester, NY, United States.; Pharmacology and Physiology Department, University of Rochester, Rochester, NY, United States.
Jazyk:	angličtina
Zdroj:	Pain [Pain] 2024 Apr 01; Vol. 165 (4), pp. 820-837. Date of Electronic Publication: 2023 Oct 26.
DOI:	10.1097/j.pain.0000000000003088
Abstrakt:	Abstract: Localized provoked vulvodynia is characterized by chronic vulvar pain that disrupts every aspect of the patient's life. Pain is localized to the vulvar vestibule, a specialized ring of tissue immediately surrounding the vaginal opening involved in immune defense. In this article, we show inflammation is the critical first step necessary for the generation of pain signals in the vulva. Inflammatory stimuli alone or combined with the transient receptor potential cation channel subfamily V member 4 (TRPV4) agonist 4α-phorbol 12,13-didecanoate stimulate calcium flux into vulvar fibroblast cells. Activity is blocked by the TRPV4 antagonist HC067047, denoting specificity to TRPV4. Using lipidomics, we found pro-resolving lipids in the vulvar vestibule were dysregulated, characterized by a reduction in pro-resolving mediators and heightened production of inflammatory mediators. We demonstrate specialized pro-resolving mediators represent a potential new therapy for vulvar pain, acting on 2 key parts of the disease mechanism by limiting inflammation and acutely inhibiting TRPV4 signaling. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)
Databáze:	MEDLINE
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