A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in Drosophila
Nociception is a neural process that animals have developed to avoid potentially tissue-damaging stimuli. While nociception is triggered in the peripheral nervous system, its modulation by the central nervous system is a critical process in mammals, whose dysfunction has been extensively implicated...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/85760 |
| _version_ | 1797785413040996352 |
|---|---|
| author | Izumi Oikawa Shu Kondo Kao Hashimoto Akiho Yoshida Megumi Hamajima Hiromu Tanimoto Katsuo Furukubo-Tokunaga Ken Honjo |
| author_facet | Izumi Oikawa Shu Kondo Kao Hashimoto Akiho Yoshida Megumi Hamajima Hiromu Tanimoto Katsuo Furukubo-Tokunaga Ken Honjo |
| author_sort | Izumi Oikawa |
| collection | DOAJ |
| description | Nociception is a neural process that animals have developed to avoid potentially tissue-damaging stimuli. While nociception is triggered in the peripheral nervous system, its modulation by the central nervous system is a critical process in mammals, whose dysfunction has been extensively implicated in chronic pain pathogenesis. The peripheral mechanisms of nociception are largely conserved across the animal kingdom. However, it is unclear whether the brain-mediated modulation is also conserved in non-mammalian species. Here, we show that Drosophila has a descending inhibitory mechanism of nociception from the brain, mediated by the neuropeptide Drosulfakinin (DSK), a homolog of cholecystokinin (CCK) that plays an important role in the descending control of nociception in mammals. We found that mutants lacking dsk or its receptors are hypersensitive to noxious heat. Through a combination of genetic, behavioral, histological, and Ca2+ imaging analyses, we subsequently revealed neurons involved in DSK-mediated nociceptive regulation at a single-cell resolution and identified a DSKergic descending neuronal pathway that inhibits nociception. This study provides the first evidence for a descending modulatory mechanism of nociception from the brain in a non-mammalian species that is mediated by the evolutionarily conserved CCK system, raising the possibility that the descending inhibition is an ancient mechanism to regulate nociception. |
| first_indexed | 2024-03-13T00:53:44Z |
| format | Article |
| id | doaj.art-f5310661bcb246f8a7356547f5eb2e95 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T00:53:44Z |
| publishDate | 2023-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f5310661bcb246f8a7356547f5eb2e952023-07-07T09:10:36ZengeLife Sciences Publications LtdeLife2050-084X2023-06-011210.7554/eLife.85760A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in DrosophilaIzumi Oikawa0Shu Kondo1Kao Hashimoto2Akiho Yoshida3https://orcid.org/0000-0001-5733-4894Megumi Hamajima4https://orcid.org/0009-0009-9425-3896Hiromu Tanimoto5Katsuo Furukubo-Tokunaga6Ken Honjo7https://orcid.org/0000-0001-7804-2436Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, JapanFaculty of Advanced Engineering, Tokyo University of Science, Katsushika-ku, Tokyo, JapanCollege of Life and Environmental Sciences, University of Tsukuba, Tsukuba, JapanGraduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, JapanCenter for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, JapanGraduate School of Life Sciences, Tohoku University, Sendai, JapanFaculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, JapanCenter for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan; Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, JapanNociception is a neural process that animals have developed to avoid potentially tissue-damaging stimuli. While nociception is triggered in the peripheral nervous system, its modulation by the central nervous system is a critical process in mammals, whose dysfunction has been extensively implicated in chronic pain pathogenesis. The peripheral mechanisms of nociception are largely conserved across the animal kingdom. However, it is unclear whether the brain-mediated modulation is also conserved in non-mammalian species. Here, we show that Drosophila has a descending inhibitory mechanism of nociception from the brain, mediated by the neuropeptide Drosulfakinin (DSK), a homolog of cholecystokinin (CCK) that plays an important role in the descending control of nociception in mammals. We found that mutants lacking dsk or its receptors are hypersensitive to noxious heat. Through a combination of genetic, behavioral, histological, and Ca2+ imaging analyses, we subsequently revealed neurons involved in DSK-mediated nociceptive regulation at a single-cell resolution and identified a DSKergic descending neuronal pathway that inhibits nociception. This study provides the first evidence for a descending modulatory mechanism of nociception from the brain in a non-mammalian species that is mediated by the evolutionarily conserved CCK system, raising the possibility that the descending inhibition is an ancient mechanism to regulate nociception.https://elifesciences.org/articles/85760nociceptionpaincholecystokinindrosulfakininneuropeptidesdescending inhibition |
| spellingShingle | Izumi Oikawa Shu Kondo Kao Hashimoto Akiho Yoshida Megumi Hamajima Hiromu Tanimoto Katsuo Furukubo-Tokunaga Ken Honjo A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in Drosophila eLife nociception pain cholecystokinin drosulfakinin neuropeptides descending inhibition |
| title | A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in Drosophila |
| title_full | A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in Drosophila |
| title_fullStr | A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in Drosophila |
| title_full_unstemmed | A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in Drosophila |
| title_short | A descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in Drosophila |
| title_sort | descending inhibitory mechanism of nociception mediated by an evolutionarily conserved neuropeptide system in drosophila |
| topic | nociception pain cholecystokinin drosulfakinin neuropeptides descending inhibition |
| url | https://elifesciences.org/articles/85760 |
| work_keys_str_mv | AT izumioikawa adescendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT shukondo adescendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT kaohashimoto adescendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT akihoyoshida adescendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT megumihamajima adescendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT hiromutanimoto adescendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT katsuofurukubotokunaga adescendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT kenhonjo adescendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT izumioikawa descendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT shukondo descendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT kaohashimoto descendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT akihoyoshida descendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT megumihamajima descendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT hiromutanimoto descendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT katsuofurukubotokunaga descendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila AT kenhonjo descendinginhibitorymechanismofnociceptionmediatedbyanevolutionarilyconservedneuropeptidesystemindrosophila |