# A new Drosophila model of astrocyte calcium signaling in chronic pain

> **NIH NIH R21** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2021 · $419,365

## Abstract

PROJECT SUMMARY
Chronic neuropathic pain is a devastating condition that significantly impacts quality of life. Better
understanding of how acute nerve injury transitions to chronic neuropathic pain is therefore a key initiative of
pain research. Transition to neuropathic pain frequently involves central sensitization, where nociceptive
networks in the central nervous system become hypersensitized to sensory inputs. During central sensitization
astrocytes become highly reactive and release excitatory and synaptogenic factors that are required for
nociceptive network sensitization. These astrocyte functions are regulated by Ca2+ signaling; however, the
specific Ca2+ signaling mechanisms required in astrocytes for neuropathic pain are poorly understood.
Astrocyte Ca2+ signaling involves somatic Ca2+ transients that traverse the entire cell body, and microdomain
Ca2+ signals localized to thin astrocytic processes. Our functional understanding of these distinct astrocyte
Ca2+ signals is limited by the complexity of mechanisms and channels that generate these signals in
mammalian astrocytes. Our proposal will directly address this by taking advantage of recent seminal findings in
Drosophila astrocytes demonstrating that somatic Ca2+ transients are mediated by the transient receptor
potential (Trp) channel Waterwitch (Wtrw) and microdomain Ca2+ signals are mediated by TrpML channels.
This provides us the means, for the first time, to genetically separate somatic and microdomain Ca2+ signals.
We will combine this with a newly developed, adult Drosophila model of centrally mediated neuropathic pain. In
Aim 1, we will determine how suppression of wtrw and trpml affects the development of neuropathic pain in
adult Drosophila. In Aim 2, we will directly analyze somatic and microdomain Ca2+ signals in adult Drosophila
astrocytes following acute injury. These experiments will allow us to clearly define the specific Ca2+ signaling
mechanisms in astrocytes that drive neuropathic pain. This will represent an important breakthrough in our
understanding of neuropathic pain etiology and may inform new pain therapeutic development.

## Key facts

- **NIH application ID:** 10196246
- **Project number:** 1R21NS121821-01
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Jeremy Thomas Smyth
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $419,365
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196246

## Citation

> US National Institutes of Health, RePORTER application 10196246, A new Drosophila model of astrocyte calcium signaling in chronic pain (1R21NS121821-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10196246. Licensed CC0.

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