# Investigating the Neural Circuits of Itch

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $532,604

## Abstract

PROJECT DESCRIPTION
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 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 the dynorphin. However, the neurons that respond to dynorphin — those that express KOR —
remained unknown, and the neural circuits through which KOR agonists inhibit itch were 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:** 9868888
- **Project number:** 5R01AR063772-08
- **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:** $532,604
- **Award type:** 5
- **Project period:** 2013-02-11 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868888

## Citation

> US National Institutes of Health, RePORTER application 9868888, Investigating the Neural Circuits of Itch (5R01AR063772-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9868888. Licensed CC0.

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