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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Drosophila / physiology*
  • Drosophila / radiation effects
  • Drosophila Proteins / metabolism
  • Electrophysiological Phenomena
  • Hedgehog Proteins / metabolism*
  • Hot Temperature
  • Nociceptors / physiology*
  • Receptors, Neurotransmitter / metabolism
  • Signal Transduction*
  • Tachykinins / metabolism*

Substances

  • Drosophila Proteins
  • Hedgehog Proteins
  • Receptors, Neurotransmitter
  • Tachykinins
  • TkR99D protein, Drosophila