Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice
The rostral ventromedial medulla (RVM) is important in descending modulation of spinal nociceptive transmission, but it is unclear if the RVM also modulates spinal pruriceptive transmission. RVM ON cells are activated by noxious algesic and pruritic stimuli and are pronociceptive. Many RVM-spinal pr...
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| Format: | Article |
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eLife Sciences Publications Ltd
2022-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/69626 |
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| author | Taylor Follansbee Dan Domocos Eileen Nguyen Amanda Nguyen Aristea Bountouvas Lauren Velasquez Mirela Iodi Carstens Keiko Takanami Sarah E Ross Earl Carstens |
| author_facet | Taylor Follansbee Dan Domocos Eileen Nguyen Amanda Nguyen Aristea Bountouvas Lauren Velasquez Mirela Iodi Carstens Keiko Takanami Sarah E Ross Earl Carstens |
| author_sort | Taylor Follansbee |
| collection | DOAJ |
| description | The rostral ventromedial medulla (RVM) is important in descending modulation of spinal nociceptive transmission, but it is unclear if the RVM also modulates spinal pruriceptive transmission. RVM ON cells are activated by noxious algesic and pruritic stimuli and are pronociceptive. Many RVM-spinal projection neurons express the neurokinin-1 receptor (Tacr1), and ON-cells are excited by local administration of substance P (SP). We hypothesized that Tacr1-expressing RVM ON cells exert an inhibitory effect on itch opposite to their pronociceptive action. Intramedullary microinjection of SP significantly potentiated RVM ON cells and reduced pruritogen-evoked scratching while producing mild mechanical sensitization. Chemogenetic activation of RVM Tacr1-expressing RVM neurons also reduced acute pruritogen-evoked scratching. Optotagging experiments confirmed RVM Tacr1-expressing neurons to be ON cells. We conclude that Tacr1-expressing ON cells in RVM play a significant role in the modulation of pruriceptive transmission. |
| first_indexed | 2024-04-12T02:52:09Z |
| format | Article |
| id | doaj.art-baa6e8ba51f6423297cb12d62cfa5c9c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:52:09Z |
| publishDate | 2022-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-baa6e8ba51f6423297cb12d62cfa5c9c2022-12-22T03:50:57ZengeLife Sciences Publications LtdeLife2050-084X2022-08-011110.7554/eLife.69626Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in miceTaylor Follansbee0https://orcid.org/0000-0002-4470-9324Dan Domocos1Eileen Nguyen2Amanda Nguyen3Aristea Bountouvas4Lauren Velasquez5Mirela Iodi Carstens6Keiko Takanami7Sarah E Ross8https://orcid.org/0000-0003-2593-3133Earl Carstens9https://orcid.org/0000-0003-4696-8116Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States; Department of Neuroscience, Johns Hopkins University, Baltimore, United StatesDepartment of Anatomy, Animal Physiology and Biophysics, University of Bucharest, Bucharest, RomaniaPittsburgh Center for Pain Research and Department of Neurobiology, University of Pittsburgh, Pittsburgh, United StatesDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United StatesDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United StatesDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United StatesDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United StatesDepartment of Environmental Life Science, National Nara Women University, Nara, JapanPittsburgh Center for Pain Research and Department of Neurobiology, University of Pittsburgh, Pittsburgh, United StatesDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United StatesThe rostral ventromedial medulla (RVM) is important in descending modulation of spinal nociceptive transmission, but it is unclear if the RVM also modulates spinal pruriceptive transmission. RVM ON cells are activated by noxious algesic and pruritic stimuli and are pronociceptive. Many RVM-spinal projection neurons express the neurokinin-1 receptor (Tacr1), and ON-cells are excited by local administration of substance P (SP). We hypothesized that Tacr1-expressing RVM ON cells exert an inhibitory effect on itch opposite to their pronociceptive action. Intramedullary microinjection of SP significantly potentiated RVM ON cells and reduced pruritogen-evoked scratching while producing mild mechanical sensitization. Chemogenetic activation of RVM Tacr1-expressing RVM neurons also reduced acute pruritogen-evoked scratching. Optotagging experiments confirmed RVM Tacr1-expressing neurons to be ON cells. We conclude that Tacr1-expressing ON cells in RVM play a significant role in the modulation of pruriceptive transmission.https://elifesciences.org/articles/69626itchdescending modulationpainRVM |
| spellingShingle | Taylor Follansbee Dan Domocos Eileen Nguyen Amanda Nguyen Aristea Bountouvas Lauren Velasquez Mirela Iodi Carstens Keiko Takanami Sarah E Ross Earl Carstens Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice eLife itch descending modulation pain RVM |
| title | Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice |
| title_full | Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice |
| title_fullStr | Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice |
| title_full_unstemmed | Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice |
| title_short | Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla in mice |
| title_sort | inhibition of itch by neurokinin 1 receptor tacr1 expressing on cells in the rostral ventromedial medulla in mice |
| topic | itch descending modulation pain RVM |
| url | https://elifesciences.org/articles/69626 |
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