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.
Highlights
DTK was not detected in class IV neurons
This study establishes that Tachykinin signaling regulates UV-induced thermal allodynia in Drosophila larvae
We speculate that Tachykinins diffuse to and bind DTKR on the plasma membrane of class IV neurons
Summary
They can act as local neurotransmitters (Salio et al, 2006) or as tonic “gain controls” on neuronal activity to modify diverse aspects of organismal physiology including appetite, biological rhythms, aggression, and more (Marder, 2012; Taghert and Nitabach, 2012). Neuropeptide signaling modulates nociception, the sensory perception of noxious stimuli. Modulation of nociception occurs following tissue damage, where the threshold that elicits aversive behaviors is reduced. This nociceptive sensitization can appear as allodynia - aversive responsiveness to previously innocuous stimuli, or hyperalgesia - exaggerated responsiveness to noxious stimuli (Gold and Gebhart, 2010). The exact roles of neuropeptides in regulating nociceptive sensitization are not yet clear
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