# Investigating the Neural Circuits of Itch

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $621,076

## Abstract

Abstract
Chronic itch severely diminishes quality of life. Although several neuronal populations that are important for itch
have been identified, we lack a population-level view of the neurons that detect itch stimuli in the dorsal root
ganglia (DRG), integrate itch in the dorsal horn, and convey itch to the brain. Moreover, although kappa opioid
receptor (KOR) agonists inhibit itch, we do not yet have a clear understanding of the neural basis of the inhibition
of itch. We propose to bridge these critical gaps in knowledge with 2-photon (2P) Ca2+ imaging of neural
populations that are engaged in response to itch and those that are inhibited by KOR agonists. A network view
of how pruritic information is initially integrated—and where KOR agonists act to inhibit this circuitry—will provide
key insight into the neural coding of itch, and may elucidate new avenues for treatment. Here, we propose to
use 2P Ca2+ imaging in the ex vivo somatosensory preparation to define the neurons that are engaged by three
types of disease-relevant itch: urticaria from mass cell degranulation, the AEW model of dry skin itch, and the
SADBE model of contact dermatitis. In Aim 1 we will characterize the DRG neurons that mediate itch; in Aim 2
we will characterize the corresponding responses of spinal excitatory neurons and spinal projection neurons;
and in Aims 3 we will analyze how this pattern of activity is altered in the presence of a KOR agonist, which
inhibits itch. Overall, we will test the hypothesis that distinct types of itch engage common excitatory interneurons
and common spinal output neurons, and that KOR agonists reduce activity in one or more of these populations,
including spinal output neurons. These experiments will provide new insight into the neural circuits that mediate
disease-relevant itch and how this circuitry can be inhibited by KOR agonists through a population view of the
neurons that detect itch in the periphery, integrate itch in the dorsal horn, and convey itch to the brain.

## Key facts

- **NIH application ID:** 10825605
- **Project number:** 5R01AR063772-12
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** H Richard Koerber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $621,076
- **Award type:** 5
- **Project period:** 2013-02-11 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825605

## Citation

> US National Institutes of Health, RePORTER application 10825605, Investigating the Neural Circuits of Itch (5R01AR063772-12). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10825605. Licensed CC0.

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