# Enteric glia and visceral pain

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2024 · $454,135

## Abstract

PROJECT SUMMARY
Abdominal pain is the most common gastrointestinal issue and is a major feature of irritable bowel syndrome
and inflammatory bowel disease. Visceral hypersensitivity has emerged as a key pathophysiological mechanism
for pain, but effective therapies are limited because the causal mechanisms whereby nociceptors become
sensitized remain largely unresolved, are heterogeneous, sexually dimorphic, and influenced by inflammation
and experiencing adverse early life events. Recent data show that enteric glia exhibit bi-directional
communication with nociceptors and alter sensory transduction during acute and chronic inflammation. The
overall goal of this proposal is to define glial mechanisms that sensitize visceral nerve fibers in a context and
sex-specific manner. This proposal tests the central hypothesis that enteric glia promote visceral hypersensitivity
through sexually dimorphic mechanisms that are influenced by acute inflammation and early life adversity. This
dual hypothesis will be tested in two specific aims that utilize glial and nociceptor calcium imaging, glial
chemogenetics, novel transgenic lines to perturb glial signaling mechanisms, and models of visceral pain driven
by acute inflammation and early life adversity. Aim 1 will use the DNBS colitis model to test the hypothesis that
enteric glia regulate visceral hypersensitivity through sexually dimorphic mechanisms during acute inflammation.
Aim 1.1 will involve cellular imaging studies where GCaMPs are expressed in nociceptive nerves or glia, glial
chemogenetics, in vitro measurements of gliotransmitter release, and in vivo visceromotor response recordings
to test the hypothesis that glia contribute to female susceptibility in visceral nociception by exhibiting greater
sensing, signal transduction, and transmitter release mechanisms than males. Aim 1.2 will use novel conditional
glial gene ablation models to test the hypothesis that differences in how glia control endocannabinoids and
histamine promote sex differences in susceptibility to developing pain following acute inflammation. Aim 2 will
use the neonatal maternal separation stress model to test the hypothesis that early life adversity promotes male
biased visceral hypersensitivity through a pathophysiological shift in gliotransmission. Aim 2.1 will use glial and
nociceptor GCaMP models in cellular imaging studies, in vitro measurements of gliotransmitter release, and in
vivo visceromotor response recordings to test the hypothesis that early life stress causes a shift from
physiological to pathophysiological gliotransmission mechanisms in males. Aim 2.2 will use protein and RNA
labeling, glial gene ablation models, cellular imaging and in vivo visceromotor recordings to test the hypothesis
that increased glial endocannabinoid degradation and decreased histamine clearance contribute to male biased
pain following early life adversity. The results of this study will provide novel insight into glial mechanisms that
regu...

## Key facts

- **NIH application ID:** 10794536
- **Project number:** 2R01DK120862-05A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** BRIAN D. GULBRANSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $454,135
- **Award type:** 2
- **Project period:** 2024-03-01 → 2028-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10794536

## Citation

> US National Institutes of Health, RePORTER application 10794536, Enteric glia and visceral pain (2R01DK120862-05A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10794536. Licensed CC0.

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