# Activating Peripheral Glia to Relieve Visceral Pain in Animal Models of Urological Chronic Pelvic Pain Syndrome (UCPPS)

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $342,100

## Abstract

PROJECT SUMMARY/ABSTRACT
There are significant gaps in our knowledge of how peripheral GFAP+ glia regulate sensory neuronal activity
and their involvement in primary afferent sensitization. The lack of understanding of the roles of peripheral glial
cells, mainly due to our inability of selectively perturbing signaling pathways in subpopulations of peripheral glia
in vivo, presents an important obstacle in developing creative and effective strategies for investigating glial
contribution in chronic diseases. The long-term goal of this project is to target GFAP+ satellite glial cells (SGCs)
for gene therapies for preventing and treating peripheral sensitization. The objective of this proposal is to
identify signaling pathways underlying SGC-neuron interaction in the sensory ganglia, as well as to
characterize the translatome changes in sensory SGC signaling involved in visceral pain and bladder
dysfunction. Strong preliminary data and past findings in sensory SGCs in the context of chronic pain led to the
central hypothesis that Gq-GPCR signaling in SGCs potently decreases the excitability and activity in bladder-
projecting sensory neurons and contributes to neural control of bladder functions. This hypothesis will be
tested by pursuing three specific aims: 1) Test the hypothesis that sensory satellite glial Gq-GPCR signaling
decreases bladder afferent sensitivity and alters micturition in physiological conditions and in inflammation-
induced visceral pain and bladder overactivity model; 2) Identify the molecular link between satellite glial Gq-
GPCR activation and decreased sensory neuronal excitability; and 3) Discover the changes in sensory satellite
glial translatome during the onset and chronic phase of inflammation-induced pelvic pain and lower urinary
tract symptoms (LUTS). Under the first aim, targeted and selective gene manipulation in peripheral GFAP+ glia
will be utilized to study the role of SGCs in physiological and pathological regulation of bladder afferent
excitability. In the second aim, the cellular and molecular mechanism underlying SGC-neuron interaction will
be identified in sensory ganglia explants using approaches similar to those used in studying CNS glial-neuronal
interactions in situ. Additional experiments will be performed in vivo to test the therapeutic potential of targeting
the identified signaling pathway(s) for alleviating visceral pain and bladder overactivity in this aim. Under the
third aim, TRAP technology will be employed to identify changes in sensory SGC translatome as a function of
inflammation-induced bladder overactivity and pelvic painin a non-biased manner.The proposed research is
significant because 1) it demonstrates a new pharmacogenetic approach for selectively activating peripheral
glia in vivo, which benefits broader research community in Neuro-urology research; 2) it is expected to fill the
knowledge gap on glial modulation of bladder function, a completely unexplored research field with high
ther...

## Key facts

- **NIH application ID:** 10454295
- **Project number:** 5R01DK129260-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Xiaoqiao Xie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $342,100
- **Award type:** 5
- **Project period:** 2021-07-19 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454295

## Citation

> US National Institutes of Health, RePORTER application 10454295, Activating Peripheral Glia to Relieve Visceral Pain in Animal Models of Urological Chronic Pelvic Pain Syndrome (UCPPS) (5R01DK129260-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10454295. Licensed CC0.

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