Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States; Department of Neuroscience, Johns Hopkins University, Baltimore, United States
Dan Domocos
Department of Anatomy, Animal Physiology and Biophysics, University of Bucharest, Bucharest, Romania
Eileen Nguyen
Pittsburgh Center for Pain Research and Department of Neurobiology, University of Pittsburgh, Pittsburgh, United States
Amanda Nguyen
Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Aristea Bountouvas
Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Lauren Velasquez
Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Mirela Iodi Carstens
Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Keiko Takanami
Department of Environmental Life Science, National Nara Women University, Nara, Japan
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.
