TY - JOUR
T1 - Inflammation, lipid dysregulation, and transient receptor potential cation channel subfamily V member 4 signaling perpetuate chronic vulvar pain
AU - Bekauri, Tamari
AU - Fischer, Sarah
AU - Honn, Kenneth V.
AU - Maddipati, Krishna Rao
AU - Love, Tanzy
AU - Little, Chantelle
AU - Wood, Ronald W.
AU - Bonham, Adrienne D.
AU - Linder, Mitchell A.
AU - Yule, David I.
AU - Emanuelle, Chrysilla
AU - Falsetta, Megan L.
N1 - Publisher Copyright:
© 2024 Lippincott Williams and Wilkins. All rights reserved.
PY - 2024/4/1
Y1 - 2024/4/1
N2 - 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.
AB - 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.
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U2 - 10.1097/j.pain.0000000000003088
DO - 10.1097/j.pain.0000000000003088
M3 - Article
C2 - 37889581
AN - SCOPUS:85180258048
SN - 0304-3959
VL - 165
SP - 820
EP - 837
JO - Pain
JF - Pain
IS - 4
ER -