# Dissection of a new spinal cord circuit in pain sensation

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $492,388

## Abstract

Nociception, or the sense of noxious stimuli, is essential for our daily lives. Normal acute nociception prevents
us from potential damage or repetitive injuries, while distorted neural circuits in pathological conditions gener-
ate chronic pain, which is a huge human health problem. At present, our understanding of neural circuits in
mediating and modulating pain sensation under normal and pathological conditions is surprisingly incomplete.
We proposed to study a population of inhibitory dorsal spinal cord interneurons, which express the receptor
tyrosine kinase RET neonatally and makes up about one third of inhibitory interneurons in laminae III to V
(deep layer). Our preliminary study showed that these deep layer early RET+ inhibitory interneurons are unique
and their circuits and functions in nociception have not been defined before.
Aim 1. Define molecular, physiological, and anatomical properties of deep layer early RET+ inhibitory
interneurons. In this aim, we will genetically label deep layer early RET+ inhibitory interneurons to study their
gross anatomy, identities of inhibitory neural transmitter, physiological properties, and single neuron morpholo-
gy. Our anticipated results will reveal unique features of deep layer early RET+ inhibitory interneurons and pro-
vide an insight into their potential connections and functions.
Aim 2. Dissect neural circuits associated with deep layer early RET+ inhibitory interneurons. In this aim,
we will use both light/electronic microscopy imaging and spinal cord slice recording coupled with electric and
optical stimuli to determine input and output of deep layer early RET+ inhibitory interneurons. Together, our
work will reveal functional connections associated with this new population of DH inhibitory interneurons.
Aim 3. Determine functions of deep layer early RET+ inhibitory interneurons in acute pain and chronic
pain. In this aim, we will either ablate deep layer early RET+ inhibitory interneurons using toxin or acutely acti-
vate them using optogenetic and pharmacological approach and test mouse nociceptive behavioral responses
under acute and chronic pain conditions. With these experiments, we anticipate revealing important functions
of deep layer early RET+ inhibitory interneurons in modulating acute and chronic pain.
In short, our proposed study will elucidate circuits and function of a new population of DH inhibitory interneu-
rons in governing the transmission and modulation of nociceptive information. Our work would lead to a better
understanding about DH circuits and provide potential new thoughts for chronic pain treatment.

## Key facts

- **NIH application ID:** 9973178
- **Project number:** 5R01NS094224-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Wenqin Luo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $492,388
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973178

## Citation

> US National Institutes of Health, RePORTER application 9973178, Dissection of a new spinal cord circuit in pain sensation (5R01NS094224-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9973178. Licensed CC0.

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