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Elife. 2015 Nov 17;4:e10735. doi: 10.7554/eLife.10735.

Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila.

Author information

1
Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States.
2
Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States.
3
Genes and Development Graduate Program, University of Texas Graduate School of Biomedical Sciences, Houston, United States.
4
Neuroscience Graduate Program, University of Texas Graduate School of Biomedical Sciences, Houston, United States.

Abstract

Pain signaling in vertebrates is modulated by neuropeptides like Substance P (SP). To determine whether such modulation is conserved and potentially uncover novel interactions between nociceptive signaling pathways we examined SP/Tachykinin signaling in a Drosophila model of tissue damage-induced nociceptive hypersensitivity. Tissue-specific knockdowns and genetic mutant analyses revealed that both Tachykinin and Tachykinin-like receptor (DTKR99D) are required for damage-induced thermal nociceptive sensitization. Electrophysiological recording showed that DTKR99D is required in nociceptive sensory neurons for temperature-dependent increases in firing frequency upon tissue damage. DTKR overexpression caused both behavioral and electrophysiological thermal nociceptive hypersensitivity. Hedgehog, another key regulator of nociceptive sensitization, was produced by nociceptive sensory neurons following tissue damage. Surprisingly, genetic epistasis analysis revealed that DTKR function was upstream of Hedgehog-dependent sensitization in nociceptive sensory neurons. Our results highlight a conserved role for Tachykinin signaling in regulating nociception and the power of Drosophila for genetic dissection of nociception.

KEYWORDS:

D. melanogaster; Hedgehog; Substance P; Trp channels; electrophysiology; neuropeptides; neuroscience; nociceptive sensitization

PMID:
26575288
PMCID:
PMC4739760
DOI:
10.7554/eLife.10735
[Indexed for MEDLINE]
Free PMC Article

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