# TLR Transduction of Dysbiotic Pelvic Pain

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $586,316

## Abstract

Chronic pelvic pain is debilitating and afflicts millions of patients in the U.S., yet pelvic pain
etiologies and effective therapies remain elusive. Microglia are CNS immune cells that play
significant roles in pain and are poised to respond to changes in microbiota, yet the roles of
microglia in pelvic pain are not fully described. Similarly, the microbiome influences many
biological processes and is recently appreciated to modulate pain, and we have identified gut
dysbiosis in pelvic pain patients and clinically relevant mouse models of pelvic pain. Microglia can
transduce microbiome signals by virtue of Toll-like receptors, but their roles in mediating pelvic
pain modulation by microbiota have not been explored. Here, we will evaluate the role of
microglia responses to microbiota in clinically-relevant models of pelvic pain. We hypothesize
that TLR4 mediates microglial responses to gut microbiota. We will test this hypothesis using two
clinically relevant mouse models of distinct underlying mechanisms that mimic postulated
etiologies of urologic pelvic pain, an infection model and a genetic susceptibility model. In Aim
1, we will quantify the role of microglia in rodent correlates of pain responses and cognitive
function and define microglial phenotypes. In Aim 2, we will define the role of TLR4 in microglia-
mediated pain. And in Aim 3, we will examine microglial responses to microbiota. Together, these
rigorous and innovative studies will provide the first characterization of TLR4 in microglia-
dependent pelvic pain responses to microbiota and thus pave the way for future probiotic
strategies for the treatment of urologic chronic pelvic pain.

## Key facts

- **NIH application ID:** 10737191
- **Project number:** 1R01DK134817-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** David J Klumpp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $586,316
- **Award type:** 1
- **Project period:** 2023-08-21 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737191

## Citation

> US National Institutes of Health, RePORTER application 10737191, TLR Transduction of Dysbiotic Pelvic Pain (1R01DK134817-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10737191. Licensed CC0.

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