# Microglia-Mediated Astrocyte Activation in the Acute-to-Chronic Pain Transition

> **NIH NIH F32** · STANFORD UNIVERSITY · 2023 · $69,080

## Abstract

PROJECT SUMMARY
While acute pain is an important biological signal in response to injured tissue, chronic pain occurs when the
pain signaling outlasts the initial injury and has deleterious effects on health and quality of life. Chronic pain
represents an enormous public health burden with few therapeutic options. Chronic pain is distinct from acute
pain with several unique features including long-lasting activation of astrocytes. Astrocytes are CNS cells with
diverse functions including energy homeostasis, regulation of the blood brain barrier, clearance of
neurotransmitters, and regulation of synaptic transmission, all of which are altered in activated states.
Preventing activation of astrocytes represents a key therapeutic target. Microglia, the resident immune cells of
the CNS, have been implicated as key mediators of astrocyte activation. In this way, microglia manipulation
may provide a tool to prevent or alter astrocyte activation, which in turn may prevent pain from becoming
chronic. Previous research from our lab has shown that depletion of microglia at the time of transition from
acute pain to chronic pain prevents chronic pain. However, when microglia are depleted once chronic pain is
established, there are only transient improvements in pain-like behaviors. One explanation for these different
effects is that microglia may be contributing indirectly to chronic pain by triggering astrocyte activation during
the transition to chronic pain. However, once astrocytes are activated, microglia cease to have an active role in
pain signaling and the alterations in spinal cord circuits maintaining chronic pain are due to changes in
astrocyte function. I hypothesize that at the acute-to-chronic transition microglia are necessary and sufficient to
activate astrocytes and that microglia effects in chronic pain are entirely dependent on astrocyte activation. In
Aim 1, I will characterize astrocyte activation in a mouse model of pain-producing peripheral injury after
selective depletion of microglia at the acute-to-chronic pain transition. I will further use DREADDs to
exogenously activate astrocytes at the acute-to-chronic transition to determine if exogenous activation of
astrocytes is sufficient to maintain the transition to chronic pain in the context of microglia depletion. In Aim 2, I
will use exogenous activation of microglia in a naïve mouse to determine if activation of microglia is sufficient to
activate astrocytes and if this activation of astrocytes leads to pain-like behaviors. Finally, in Aim 3 I will
determine which signals from microglia are important for astrocyte activation in the induction of chronic pain
using cell-cell interaction analyses of single nuclei RNA-Sequencing data from astrocytes and microglia. Using
the innovative experiments in this research proposal, I will uncover the relative roles and contributions of
microglia and astrocytes to chronic pain and generate new targets for pain therapeutics. The proposed
research i...

## Key facts

- **NIH application ID:** 10639281
- **Project number:** 1F32NS131193-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Amy Nippert
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $69,080
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10639281

## Citation

> US National Institutes of Health, RePORTER application 10639281, Microglia-Mediated Astrocyte Activation in the Acute-to-Chronic Pain Transition (1F32NS131193-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10639281. Licensed CC0.

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