# Investigating the Neural Circuits of Itch

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $232,060

## Abstract

Abstract
Persistent itch is an aversive condition that results in a severely diminished quality of life. Our
approach to address this important health issue is to gain a better understanding of the underlying
neural circuits and pathways. Specifically, we propose to investigate the mechanisms through
which kappa opioid receptor (KOR) signaling modulates itch. The long-term goal of our research
program is aimed at the development of novel interventions for itch that are both safe and
effective. We previously found that mice lacking the transcription factor Bhlhb5 show elevated
itch, and that this effect is caused by the loss of a specific population spinal inhibitory interneurons
that express dynorphin. However, the neurons that respond to dynorphin — those that express
KOR — remained unknown, and the neural circuits through which KOR agonists inhibit itch are
unclear. To address these gaps, our lab developed novel tools (KOR-Cre allele) and approaches
(ex vivo preparation) to study this circuitry. We also discovered that in models of pathological itch
there is abnormal bursting behavior in lamina I spinal neurons. Here, we propose to elucidate the
circuitry through which KOR agonists inhibit itch, combining anatomical (AIM 1), behavioral (AIM
2), physiological (AIM 3), and translational (AIM 4) approaches. Our overall hypothesis is that
KOR signaling acts on both primary afferents and spinal neurons to inhibit acute pruritoception,
and that KOR agonists will continue to be effective in the presence of persistent itch. Our proposal
is innovative because it combines these state-of-the-art tools and approaches to elucidate the
neural circuits through which KOR agonists inhibit pruritoception. The combination of conceptual
advances and therapeutic insight into the neural circuitry through which KOR agonists inhibit itch
makes this proposal highly significant to human health.

## Key facts

- **NIH application ID:** 10049335
- **Project number:** 3R01AR063772-08S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sarah Elizabeth Ross
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $232,060
- **Award type:** 3
- **Project period:** 2013-02-11 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049335

## Citation

> US National Institutes of Health, RePORTER application 10049335, Investigating the Neural Circuits of Itch (3R01AR063772-08S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10049335. Licensed CC0.

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