# Enteric glia and visceral pain

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2021 · $403,740

## Abstract

ABSTRACT
Abdominal pain is the most common gastrointestinal issue and is a major cause of suffering in functional
gastrointestinal disorder such as irritable bowel syndrome (IBS) and in the inflammatory bowel diseases (IBD).
Despite extensive efforts, there is still no consensus regarding the mechanisms responsible for producing
abdominal pain. This lack of progress is reflected by the poor efficacy of current therapies and the stalled
progress toward novel, targeted therapies for abdominal pain. The overall goal of this proposal is to understand
mechanisms that sensitize visceral nerve fibers and the specific focus of this proposal is on mechanisms
regulated by enteric glia. Glia play a central role in the regulation of pain transmission in the central nervous
system, but how interactions between glia and nerve fibers in the intestine contribute to the generation of
visceral pain is unknown. This proposal tests the central hypothesis that enteric glia contribute to visceral
hypersensitivity by direct interactions with nociceptors, and indirectly by modulating immune responses. This
dual hypothesis will be tested in two specific aims that utilize targeted genetic models to manipulate glia,
established animal models of visceral hypersensitivity, and optogenetic recordings, immunohistochemical
assays, electrophysiology, and visceromotor reflex recordings to study the impact on sensory neuron activity in
health and disease. Aim 1 will test the hypothesis that enteric glia directly modulate the activity of visceral
nociceptors. Specific Aim 1a will use chemogenetic and knockout mouse models to study the role of
gliotransmitter release and Specific Aim 1b will use selective drugs and knockout mice to study the role of glial
ectoenzymes that regulate ATP and histamine availability. Aim 2 will test the hypothesis that enteric glia
indirectly modulate visceral nociceptors through interactions with immune cells. Specific Aim 2a will use
transgenic mice and monoclonal antibodies to study glial interactions with macrophages mediated by the
release of mediators including ATP and M-CSF. Specific Aim 2b will use knockout mice and monoclonal
antibodies to study interactions that are secondarily dependent on interactions between glia and lymphocytes
mediated by antigen presentation. Immune responses in Aim 2 will be analyzed by microarrays,
immunohistochemistry, and flow cytometry. The results of this study will identify novel effects of glial–immune
interactions on sensory neurons in the periphery. This new insight into mechanisms that sensitize visceral
nerves will facilitate the development of new therapies for abdominal pain in functional gastrointestinal
disorders, such as IBS and IBD.

## Key facts

- **NIH application ID:** 10112902
- **Project number:** 5R01DK120862-03
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** BRIAN D. GULBRANSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,740
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112902

## Citation

> US National Institutes of Health, RePORTER application 10112902, Enteric glia and visceral pain (5R01DK120862-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10112902. Licensed CC0.

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