# The impact of hormonal modulation on systemic inflammation and central sensitization

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $634,460

## Abstract

Abstract. Chronic pelvic pain remains a challenging condition to treat, in large part because underlying
disease mechanisms are poorly understood. Endometriosis-associated pelvic pain (EAPP) is a common form
of CPP wherein the severity of disease is only weakly associated with the degree of pain experienced. While
pelvic inflammation is a well-established contributing factor to EAPP, we propose that low-grade systemic
inflammation also contributes to the disease state by promoting central nervous system (CNS) sensitization.
Emerging evidence from our group and others suggests that low-grade systemic inflammation can promote
multiple aspects of CNS sensitization including clinical manifestations (comorbid pain conditions, widespread
pain), hypersensitivity to experimental stimuli, and altered brain functional connectivity in pelvic pain. While
hormonal suppression is effective for many women, and acts in part by dampening estradiol-dependent pelvic
inflammation, little is known about the relative contributions of low-grade systemic inflammation and CNS
sensitization to EAPP. We propose to use the FDA-approved, gonadotropin releasing hormone receptor
antagonist, elagolix, available in two dosages, as a mechanistic probe to assess the effects of pelvic and
systemic inflammation on EAPP. The presence of robust dose-dependent effects on EAPP and its comorbid
symptoms suggests to us that the higher dose also reduces CNS sensitization, possibly due to reduced
systemic inflammation. To investigate this hypothesis, we will conduct a double-blind, placebo controlled
randomized clinical trial in which 200 women with EAPP will be randomly assigned to low-dose (150mg daily)
or high-dose (400mg daily) elagolix or placebo with evaluation of pain mechanism outcomes prior to and after
treatment. We will focus on two common patient phenotypes – those with EAPP only and those with EAPP
and widespread pain (1:1 recruitment). In Aim 1, we will first define the relationship between pelvic
inflammation, systemic inflammation, and CNS sensitization using well-vetted neurobiological measures of
CNS sensitization. We anticipate that systemic inflammation will be associated with CNS sensitization, while
pelvic inflammation will not be. In Aim 2, we will identify dose-dependent changes in CNS sensitization as well
as systemic and pelvic inflammation during hormonal suppression for EAPP through the above-described
clinical trial. We anticipate that both dosages will improve pelvic inflammation, but that systemic inflammation
and CNS sensitization will be improved on high-dose elagolix. We furthermore anticipate that those with
widespread pain will be more likely to respond to high-dose elagolix. In an exploratory Aim 3, we will
determine if baseline levels of pelvic and/or systemic inflammatory activity, as well as CNS sensitization,
predict the response to elagolix. These studies are critical to develop alternative mechanistic models of pain
promotion and relief in this vul...

## Key facts

- **NIH application ID:** 10932848
- **Project number:** 5R01HD108253-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Sawsan As-Sanie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $634,460
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932848

## Citation

> US National Institutes of Health, RePORTER application 10932848, The impact of hormonal modulation on systemic inflammation and central sensitization (5R01HD108253-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932848. Licensed CC0.

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