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Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla

View ORCID ProfileTaylor Follansbee, View ORCID ProfileDan Domocos, View ORCID ProfileEileen Nguyen, Amanda Nguyen, Aristea Bountouvas, Lauren Velasquez, Mirela Iodi Carstens, View ORCID ProfileKeiko Takanami, Sarah E. Ross, E. Carstens
doi: https://doi.org/10.1101/2021.04.06.438701
Taylor Follansbee
1Department of Neurobiology, Physiology and Behavior, Univ. of California, Davis CA 95616, USA
2Department of Neuroscience, Johns Hopkins University, Baltimore MD 21205
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  • For correspondence: tfollansbee@ucdavis.edu
Dan Domocos
3Department of Anatomy, Animal Physiology and Biophysics, University of Bucharest, Bucharest, Romania
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Eileen Nguyen
4Pittsburgh Center for Pain Research and Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA
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Amanda Nguyen
1Department of Neurobiology, Physiology and Behavior, Univ. of California, Davis CA 95616, USA
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Aristea Bountouvas
1Department of Neurobiology, Physiology and Behavior, Univ. of California, Davis CA 95616, USA
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Lauren Velasquez
1Department of Neurobiology, Physiology and Behavior, Univ. of California, Davis CA 95616, USA
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Mirela Iodi Carstens
1Department of Neurobiology, Physiology and Behavior, Univ. of California, Davis CA 95616, USA
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Keiko Takanami
5Dept. of Environmental Life Science, National Nara Women University, Nara Japan
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Sarah E. Ross
4Pittsburgh Center for Pain Research and Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA
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E. Carstens
1Department of Neurobiology, Physiology and Behavior, Univ. of California, Davis CA 95616, USA
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Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 15, 2022.
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Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla
Taylor Follansbee, Dan Domocos, Eileen Nguyen, Amanda Nguyen, Aristea Bountouvas, Lauren Velasquez, Mirela Iodi Carstens, Keiko Takanami, Sarah E. Ross, E. Carstens
bioRxiv 2021.04.06.438701; doi: https://doi.org/10.1101/2021.04.06.438701
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Inhibition of itch by neurokinin 1 receptor (Tacr1) -expressing ON cells in the rostral ventromedial medulla
Taylor Follansbee, Dan Domocos, Eileen Nguyen, Amanda Nguyen, Aristea Bountouvas, Lauren Velasquez, Mirela Iodi Carstens, Keiko Takanami, Sarah E. Ross, E. Carstens
bioRxiv 2021.04.06.438701; doi: https://doi.org/10.1101/2021.04.06.438701

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