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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2015-11-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/10735 |
| _version_ | 1797997474078523392 |
|---|---|
| author | Seol Hee Im Kendra Takle Juyeon Jo Daniel T Babcock Zhiguo Ma Yang Xiang Michael J Galko |
| author_facet | Seol Hee Im Kendra Takle Juyeon Jo Daniel T Babcock Zhiguo Ma Yang Xiang Michael J Galko |
| author_sort | Seol Hee Im |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T10:33:36Z |
| format | Article |
| id | doaj.art-522f8d3c8ef9484ba0c3cc37a756b006 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:33:36Z |
| publishDate | 2015-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-522f8d3c8ef9484ba0c3cc37a756b0062022-12-22T04:29:21ZengeLife Sciences Publications LtdeLife2050-084X2015-11-01410.7554/eLife.10735Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in DrosophilaSeol Hee Im0Kendra Takle1Juyeon Jo2Daniel T Babcock3Zhiguo Ma4Yang Xiang5Michael J Galko6Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, United StatesDepartment of Neurobiology, University of Massachusetts Medical School, Worcester, United StatesDepartment of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States; Genes and Development Graduate Program, University of Texas Graduate School of Biomedical Sciences, Houston, United StatesDepartment of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States; Neuroscience Graduate Program, University of Texas Graduate School of Biomedical Sciences, Houston, United StatesDepartment of Neurobiology, University of Massachusetts Medical School, Worcester, United StatesDepartment of Neurobiology, University of Massachusetts Medical School, Worcester, United StatesDepartment of Genetics, University of Texas MD Anderson Cancer Center, Houston, United States; Genes and Development Graduate Program, University of Texas Graduate School of Biomedical Sciences, Houston, United States; Neuroscience Graduate Program, University of Texas Graduate School of Biomedical Sciences, Houston, United StatesPain 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.https://elifesciences.org/articles/10735nociceptive sensitizationSubstance PHedgehogelectrophysiologyTrp channelsneuropeptide |
| spellingShingle | Seol Hee Im Kendra Takle Juyeon Jo Daniel T Babcock Zhiguo Ma Yang Xiang Michael J Galko Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila eLife nociceptive sensitization Substance P Hedgehog electrophysiology Trp channels neuropeptide |
| 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 | nociceptive sensitization Substance P Hedgehog electrophysiology Trp channels neuropeptide |
| url | https://elifesciences.org/articles/10735 |
| work_keys_str_mv | AT seolheeim tachykininactsupstreamofautocrinehedgehogsignalingduringnociceptivesensitizationindrosophila AT kendratakle tachykininactsupstreamofautocrinehedgehogsignalingduringnociceptivesensitizationindrosophila AT juyeonjo tachykininactsupstreamofautocrinehedgehogsignalingduringnociceptivesensitizationindrosophila AT danieltbabcock tachykininactsupstreamofautocrinehedgehogsignalingduringnociceptivesensitizationindrosophila AT zhiguoma tachykininactsupstreamofautocrinehedgehogsignalingduringnociceptivesensitizationindrosophila AT yangxiang tachykininactsupstreamofautocrinehedgehogsignalingduringnociceptivesensitizationindrosophila AT michaeljgalko tachykininactsupstreamofautocrinehedgehogsignalingduringnociceptivesensitizationindrosophila |