Highlights
- •Vulvodynia reduces a woman's quality of life, and new therapies are direly needed.
- •Inflammation likely plays a role in vulvodynia and represents a therapeutic target.
- •Agents that resolve inflammation reduce pro-nociceptive signals in human vulvar fibroblasts.
- •Pro-resolving agents have analgesic effects in a mouse model of vulvodynia.
- •Pro-resolving agents are a potentially noninvasive and safe therapy for vulvodynia.
Abstract
Localized provoked vulvodynia (LPV) is the most common cause of chronic dyspareunia
in premenopausal women, characterized by pain with light touch to the vulvar vestibule
surrounding the vaginal opening. The devastating impact of LPV includes sexual dysfunction,
infertility, depression, and even suicide. Yet, its etiology is unclear. No effective
medical therapy exists; surgical removal of the painful vestibule is the last resort.
In LPV, the vestibule expresses a unique inflammatory profile with elevated levels
of pro-nociceptive proinflammatory mediators prostaglandin E2 (PGE2) and interleukin-6 (IL-6), which are linked to lower mechanical sensitivity thresholds.
Specialized pro-resolving mediators (SPMs), lipids produced endogenously within the
body, hold promise as an LPV treatment by resolving inflammation without impairing
host defense. Ten of 13 commercially available SPMs reduced IL-6 and PGE2 production by vulvar fibroblasts, administered either before or after inflammatory
stimulation. Using a murine vulvar pain model, coupling proinflammatory mediator quantification
with mechanical sensitivity threshold determination, topical treatment with the SPM,
maresin 1, decreased sensitivity and suppressed PGE2 levels. Docosahexaenoic acid, a precursor of maresin 1, was also effective in reducing
PGE2 in vulvar fibroblasts and rapidly restored mouse sensitivity thresholds. Overall,
SPMs and their precursors may be a safe and efficacious for LPV.
Perspective: Vulvodynia, like many pain conditions, is difficult to treat because disease origins
are incompletely understood. Here, we applied our knowledge of more recently discovered
vulvodynia disease mechanisms to screen novel therapeutics. We identified several
specialized pro-resolving mediators as likely potent and safe for treating LPV with
potential for broader application.
Key Words
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Article info
Publication history
Published online: April 01, 2021
Accepted:
March 24,
2021
Received in revised form:
March 5,
2021
Received:
November 20,
2020
Footnotes
Disclosures: The authors have no conflicts of interest.
This work was funded by NIH-NICHD R01 HD092334 and HD069313. The Wayne State Lipidomics Core is supported in part by the National Center for Research Resources, National Institutes of Health Grant S10RR027926se mechanism.
Identification
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© 2021 by United States Association for the Study of Pain, Inc.
