# Analgesic Signaling in Drosophila

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2022 · $405,000

## Abstract

Analgesia, the dampening of nociceptive responses to noxious stimuli capable of damaging tissues, is an
adaptive behavioral response for organisms- allowing them to feel less pain in physiologically appropriate
situations such as physical trauma or the fight/flight response. Analgesia has traditionally been studied in
vertebrate models, where endogenous opioid peptides bind to their cognate receptors to dampen behavioral
responses to painful stimuli. Genetically tractable model organisms such as Drosophila have recently been used
to explore the molecular/genetic bases of nociception and nociceptive sensitization following tissue injury but
have not yet been used to dissect conserved analgesia signaling. Drosophila offer both speed of genetic analysis
and a variety of sophisticated genetic tools for analyzing gene expression and function that should prove a
valuable complement to existing experimental paradigms for the study of analgesia. Our long-term goal in this
basic research project is to identify and characterize analgesic signaling pathways in Drosophila larvae. That
such pathways are likely to exist is evidenced by our preliminary findings that the opiate compound morphine is
analgesic for Drosophila larvae and that a conserved G-protein coupled receptor (GPCR) is required in this
organism for thermal analgesia. Morphine feeding to fly larvae causes transient analgesia that spans multiple
sensory modalities (heat, cold, touch, chemical), is mimicked by other opiates (fentanyl) and is partially naloxone
reversible. Our short-term goals over the initial project period will be to characterize the GPCR required for
thermal analgesia. Using our knowledge of which tissues express the GPCR we will determine which tissues
functionally require it for analgesia, and assess whether the putative receptor’s analgesic effects extend to other
sensory modalities beyond heat. At the biochemical level we will test whether the GPCR (and it’s clearest human
ortholog) directly binds morphine to activate signaling. At the genetic level we will identify endogenous peptide
ligand(s) and probe genetic interactions with previously identified nociceptive genes and nociceptive sensitization
signaling pathways. In our final aim we will probe cellular effects of morphine administration (calcium changes)
and whether known deleterious biological side effects of morphine, development of tolerance and constipation
are also observed in our new model. Successful completion of these aims will provide a comprehensive cellular
and genetic analysis of analgesic signaling in this new model- basic information that is likely to generate testable
hypotheses for ongoing work in vertebrate models. Moving forward, this new model of analgesic signaling will
provide the possibility of unbiased gene discovery approaches that should allow for identification of novel
conserved genes required for analgesia- targets that may in some cases be potentially relevant to human and
health and worthy...

## Key facts

- **NIH application ID:** 10518586
- **Project number:** 1R01NS124606-01A1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** MICHAEL J GALKO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $405,000
- **Award type:** 1
- **Project period:** 2022-06-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518586

## Citation

> US National Institutes of Health, RePORTER application 10518586, Analgesic Signaling in Drosophila (1R01NS124606-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10518586. Licensed CC0.

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