# Vestibulodynia: Understanding Pathophysiology and Determining Appropriate Treatments (Vestibulodynia: UPDATe)

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $768,005

## Abstract

ABSTRACT
Vestibulodynia (VBD) is a chronic pelvic pain condition that affects 1 in 6 reproductive aged women, yet remains
ineffectively treated by standard trial-and-error approaches. Our group has identified two distinct VBD subtypes
that may benefit from different types of treatment: 1) VBD peripheral (VBD-p) subtype characterized by localized
pain specific to the vulvar vestibule, and 2) VBD central (VBD-c) subtype characterized by pain at both vaginal
and remote body regions. Preliminary data further demonstrate that VBD-p and VBD-c subtypes differ with
respect to patient reported outcomes (e.g., physical and mental health), production of cytokines (intracellular
proteins that regulate the activity of pain nerves and inflammatory processes), and expression of microRNAs
(small non-coding RNA molecules that regulate gene expression). Women with VBD-p exhibit normal
psychological profiles; balanced circulating pro- and anti-inflammatory cytokines; and dysregulation in
microRNAs that regulate the expression of genes in estrogen pathways. In contrast, women with VBD-c report
decreased functional status and increased somatization; increased pro-inflammatory but not anti-inflammatory
cytokines; and dysregulation in microRNAs that regulate the expression of genes relevant to muscle, nerve, and
immune cell function. Based on these data, we hypothesize that two VBD-p and VBD-c subtypes will
preferentially respond to peripheral, central, or combined treatments and can be distinguished by cytokine and
microRNA profiles. These hypotheses will be tested in a phase III clinical trial that evaluates diverse treatment
strategies in women with VBD-p and VBD-c. Participants will be randomly assigned to one of four parallel arms:
peripheral treatment with 5% lidocaine + 0.5 mg/ml estradiol compound cream, 2) central treatment with the
tricyclic antidepressant nortriptyline, 3) combined peripheral and central treatments, or 4) placebo. The treatment
phase will last 4 months (with a 6-week titration at treatment initiation and 2-week taper period at 4 months), with
outcome measures and biomarkers assessed at 4 time points (0, 2, 4, and 6 months). First, we will compare the
efficacy of treatments in alleviating pain among women with VBD-p and VBD-c using standardized tampon
insertion with a numeric rating scale and self-reported pain on the McGill Pain Questionnaire. Next, we will
compare the efficacy of treatments in improving perceived physical, mental, and sexual health among women
with VBD-p and VBD-c using standardized questionnaires. Finally, we will measure cytokines and microRNAs
in women with VBD-p versus VBD-c using multiplex assays and RNA sequencing, and determine the ability of
these biomarkers to predict treatment response. Successful completion of the proposed work will provide new
insights into the mechanisms that drive pain perception and treatment response in two distinct VBD subtypes, and
determine the efficacy of peripheral, central, and combine...

## Key facts

- **NIH application ID:** 9947980
- **Project number:** 5R01HD096331-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Andrea G Nackley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $768,005
- **Award type:** 5
- **Project period:** 2018-09-11 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947980

## Citation

> US National Institutes of Health, RePORTER application 9947980, Vestibulodynia: Understanding Pathophysiology and Determining Appropriate Treatments (Vestibulodynia: UPDATe) (5R01HD096331-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9947980. Licensed CC0.

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