# Role of NK-1 receptors in descending modulation and ascending transmission of itch

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $326,850

## Abstract

Project Summary
 Itchy skin conditions affect a substantial portion of the US population at annual costs exceeding $100
billion. Most types of chronic itch are poorly managed, establishing a compelling need to develop more
effective mechanisms-based treatments for these debilitating conditions. The present proposal will investigate
the role of neurons located in the rostral ventromedial medulla (RVM) that express the receptor for substance P
(i.e., NK-1R) in descending modulation of itch, as well as the role of NK-1R-expressing neurons in the
superficial spinal and medullary dorsal horn in the ascending transmission of itch.
 The proposal has two overarching aims. Specific Aim 1 hypothesizes that NK-1R-expressing neurons,
and specifically ON-cells in the RVM (i.e., those that fire just prior to a noxious stimulus-evoked withdrawal
response), are critically involved in descending inhibition of spinal itch transmission. We will employ
chemogenetic and intracranial microinjection approaches to test if activation of NK-1R-expressing RVM
neurons suppresses acute pruritogen-evoked itch behavior, or manifestations of chronic itch (spontaneous and
touch-evoked scratching) in mouse models of psoriasis and atopic dermatitis itch. We will also investigate NK-
1R-mediated descending inhibition of spinal itch-transmitting neurons. Finally, we will record from
optogenetically identified NK-1R-expressing neurons in RVM and functionally establish if they are ON cells.
Specific Aim 2 hypothesizes that NK-1R-expressing neurons in the superficial spinal/ medullary dorsal horn
give rise to ascending projections to the somatosensory thalamus and parabrachial nucleus that are critically
involved in transmitting itch-related signals. We will use an optogenetic approach to determine if NK-1R-
expressing neurons in the spinal/medullary dorsal horn are activated by pruritogenic stimuli, and opto- and
chemogenetic approaches to investigate if the activation of such neurons elicits behavioral signs of itch (and/or
pain). A better understanding of central itch modulation and ascending sensory transmission has translational
significance for developing novel antipruritic treatments targeting NK-1 receptors to increase descending
inhibition of itch and reduce ascending itch-related signals.
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## Key facts

- **NIH application ID:** 10227960
- **Project number:** 5R01AR076434-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** EARL E CARSTENS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $326,850
- **Award type:** 5
- **Project period:** 2020-08-05 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227960

## Citation

> US National Institutes of Health, RePORTER application 10227960, Role of NK-1 receptors in descending modulation and ascending transmission of itch (5R01AR076434-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10227960. Licensed CC0.

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