# Mechanisms of vulvodynia involving dysregulation of pro-resolving lipids

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2022 · $473,925

## Abstract

The Focus: Localized provoked vulvodynia (LPV) is the most common cause of longstanding dyspareunia
(painful sexual intercourse) in premenopausal women. Yet, LPV etiology is unclear, and no effective medical
therapy exists; clinical trials report that treatments are no better in alleviating pain than placebo. LPV presents
with pain to light touch limited to a defined region of the female lower genital tract termed the vulvar vestibule.
The Premise: Our research team has discovered that fibroblast strains isolated from painful sites in the vulvar
vestibule produce elevated levels of pro-pain and proinflammatory mediators (e.g. PGE2 and IL-6). When
exposed to proinflammatory stimuli found in the vulvovaginal milieu, vestibular fibroblasts produce significantly
higher levels of pro-pain signals than fibroblasts from pain-free sites a few millimeters away. This unique and
intrinsic responsiveness connects innate vulvar responses to neuro-inflammation and culminates in localized,
longstanding pain. Thus, LPV is likely an exacerbation of a normal anatomically-defined innate inflammatory
response. Therapeutics that resolve inflammation and pain without impairing normal host defense (i.e.
specialized pro-resolving mediators; SPMs) may be effective against LPV. SPMs are omega-3 and omega-6
fatty acid-derived lipids that consist of several types called, resolvins, maresins, protectins, and lipoxins. SPMs
are naturally produced by the human body, have virtually no toxicity, and several are in clinical trial for
inflammatory and other diseases, which could lead to faster clinical translation. Although SPMs have not been
tested as an LPV therapy, we have strong supporting evidence that these lipids will be effective against LPV.
Organizing Hypothesis: We hypothesize that SPMs will effectively modulate the LPV pathologic response
and in turn, will successfully resolve LPV-associated neuro-inflammatory pain. Here, we will identify SPMs that
are effective in reducing levels of proinflammatory mediators associated with LPV pain, define the mechanisms
whereby SPMs act, their role(s) in LPV disease, and test therapeutic candidates in a preclinical LPV model.
Specific Aim 1: Investigate the role of SPMs in blunting proinflammatory/pro-pain responses in vulvar
fibroblasts, tissues, and fluids from controls and patients with LPV.
Specific Aim 2: Determine the mechanism(s) that govern SPM production, responsiveness, and therapeutic
potential in vulvar fibroblasts.
Specific Aim 3: Evaluate the efficacy of SPMs in alleviating pain using a novel preclinical LPV mouse model.
Impact on the field: We will make a significant step forward in identifying potential therapeutic agents that
could not only reduce excessive proinflammatory signaling and pain in the context of LPV, but also in other
chronic inflammatory conditions. Furthermore, we will strengthen the methodological basis for preclinical
analgesia testing in LPV and identify SPM molecules that could be readily transla...

## Key facts

- **NIH application ID:** 10414893
- **Project number:** 5R01HD092334-05
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Constantine G HAIDARIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $473,925
- **Award type:** 5
- **Project period:** 2018-09-13 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414893

## Citation

> US National Institutes of Health, RePORTER application 10414893, Mechanisms of vulvodynia involving dysregulation of pro-resolving lipids (5R01HD092334-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10414893. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*