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Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila
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 no...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739760/ https://www.ncbi.nlm.nih.gov/pubmed/26575288 http://dx.doi.org/10.7554/eLife.10735 |
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author | Im, Seol Hee Takle, Kendra Jo, Juyeon Babcock, Daniel T Ma, Zhiguo Xiang, Yang Galko, Michael J |
author_facet | Im, Seol Hee Takle, Kendra Jo, Juyeon Babcock, Daniel T Ma, Zhiguo Xiang, Yang Galko, Michael J |
author_sort | Im, Seol Hee |
collection | PubMed |
description | 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. DOI: http://dx.doi.org/10.7554/eLife.10735.001 |
format | Online Article Text |
id | pubmed-4739760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47397602016-03-17 Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila Im, Seol Hee Takle, Kendra Jo, Juyeon Babcock, Daniel T Ma, Zhiguo Xiang, Yang Galko, Michael J eLife Neuroscience 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. DOI: http://dx.doi.org/10.7554/eLife.10735.001 eLife Sciences Publications, Ltd 2015-11-17 /pmc/articles/PMC4739760/ /pubmed/26575288 http://dx.doi.org/10.7554/eLife.10735 Text en © 2015, Im et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Im, Seol Hee Takle, Kendra Jo, Juyeon Babcock, Daniel T Ma, Zhiguo Xiang, Yang Galko, Michael J Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila |
title | Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila |
title_full | Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila |
title_fullStr | Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila |
title_full_unstemmed | Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila |
title_short | Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila |
title_sort | tachykinin acts upstream of autocrine hedgehog signaling during nociceptive sensitization in drosophila |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739760/ https://www.ncbi.nlm.nih.gov/pubmed/26575288 http://dx.doi.org/10.7554/eLife.10735 |
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