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

  1. Seol Hee Im
  2. Kendra Takle
  3. Juyeon Jo
  4. Daniel T Babcock
  5. Zhiguo Ma
  6. Yang Xiang
  7. Michael J Galko  Is a corresponding author
  1. University of Texas MD Anderson Cancer Center, United States
  2. University of Massachusetts Medical School, United States
  3. University of Wisconsin-Madison, 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.

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  1. Seol Hee Im

    Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kendra Takle

    Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Juyeon Jo

    Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel T Babcock

    Department of Genetics, University of Wisconsin-Madison, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zhiguo Ma

    Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yang Xiang

    Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael J Galko

    Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States
    For correspondence
    mjgalko@mdanderson.org
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2015, Im et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Seol Hee Im
  2. Kendra Takle
  3. Juyeon Jo
  4. Daniel T Babcock
  5. Zhiguo Ma
  6. Yang Xiang
  7. Michael J Galko
(2015)
Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila
eLife 4:e10735.
https://doi.org/10.7554/eLife.10735

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https://doi.org/10.7554/eLife.10735