# Cross Organ Mechanisms in Chronic Pelvic Pain

> **NIH NIH R01** · ENDEAVOR HEALTH CLINICAL OPERATIONS · 2024 · $619,753

## Abstract

Chronic pelvic pain (CPP) disorders cause significant distress and often lack effective treatments. Although
dysmenorrhea is closely associated with 80% of cases of CPP, little is known about why only some women
with menstrual pain go on to develop conditions like interstitial cystitis/bladder pain syndrome, irritable bowel
syndrome, or endometriosis. Intriguingly, 20% of dysmenorrhea sufferers (without chronic pain) display a key
feature of many CPP states, bladder hypersensitivity on noninvasive bladder filling, and appear on pilot studies
at higher risk of CPP in one year. In this team’s prior studies, women with the dysmenorrhea with bladder pain
phenotype (DYSB) also exhibit greater somatic symptom burden, experimental pain hypersensitivity, and
psychological dysregulation—features found in many chronic pain patients. As little is known about the acute to
CPP transition, this renewal application seeks to track pelvic pain symptomatology prospectively in DYSB
women and to expand those initial mechanistic studies. Aim 1 is a two-year longitudinal study of 1050 young
women oversampled for dysmenorrhea to find 150 DYSB cases and establish their risk trajectory for CPP
symptoms vs. those with only dysmenorrhea (DYS only = 750) and healthy controls (HC = 150). Along with a
virtual bladder filling screening test, other patient health factors potentially predicting development of CPP will
be captured, including overall pelvic experiences and general sensory sensitivity. Aim 2 will investigate 100
DYSB and 100 controls (DYS only and HC) on two dimensions of CPP mechanistically—bladder
hypersensitivity and multimodal hypersensitivity (a composite of experimentally evoked responses to
nonvisceral quantitative sensory tests [QST]). Electroencephalography-based studies will further investigate
which neurological mechanisms (i.e. ascending neural hyperexcitability, descending inhibition, and neural
oscillations) underlie these two components and predict one-year worsening of CPP symptoms. Aim 3 studies
whether another key mechanism of pain sensitization, Toll-like Receptor-4 inflammatory reactivity, influences
CPP progression, using an integrated whole-blood collection and leukocyte culture system. This renewal
application significantly extends this discovery of an at-risk phenotype by providing a method for
expanding screening and characterizing reversible mechanisms. This essential followup study utilizes
innovative combinations of QST with EEG measurements of brain activity to identify the mechanisms
responsible for CPP-related-sensory abnormalities, alongside measures of systemic inflammatory
reactivity that are strongly implicated in sensory hypersensitivity. Notably, if these are confirmed,
candidate early interventions already exist to modulate these mechanisms, including mindfulness meditation
and consistent anti-inflammatory use for dysmenorrhea. Successful completion of these studies would
accelerate efforts to prevent the transition from acute ...

## Key facts

- **NIH application ID:** 10840347
- **Project number:** 5R01DK100368-07
- **Recipient organization:** ENDEAVOR HEALTH CLINICAL OPERATIONS
- **Principal Investigator:** Frank Fu-sheng Tu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $619,753
- **Award type:** 5
- **Project period:** 2023-05-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840347

## Citation

> US National Institutes of Health, RePORTER application 10840347, Cross Organ Mechanisms in Chronic Pelvic Pain (5R01DK100368-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10840347. Licensed CC0.

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