# Functional and genetic characterization of human DRG and spinal cord at single cell resolution

> **NIH NIH U19** · WASHINGTON UNIVERSITY · 2024 · $488,329

## Abstract

Specific Aims: Tens of millions of Americans suffer from chronic pain. Unfortunately for these patients, there
is very little we can offer in the way of treatments. Opioids represent the main tool for treating pain, but their use
in chronic pain conditions suffers from a poor evidence base and the inherent risk of addiction. The current crisis
of opioid-related deaths highlights the risk associated with widespread opioid use. The parallel crises of chronic
pain and opioid-related deaths has led the NIH to launch the HEAL Initiative, with one of the major goals being
the identification of novel analgesics for the treatment of pain, with a focus on drugs that are non-addicting. The
PRECISION Human Pain Network seeks to provide foundational data on the diversity among cell types that
comprise the pain neuraxis. Goals for our proposed PRECISION Human Pain Network U19 center include the
development of optimized experimental protocols and functional assays utilizing primary human cells and tissue
(including dorsal root ganglion neurons and spinal cord slices), and the elucidation of comprehensive
molecular/cellular phenotypes that underlie human pain transduction, transmission, and processing under
different pain conditions. This project seeks to increase our understanding of the physiological properties of
human neurons in the pain neuraxis. The three aims here will begin to catalog the functional profiles and
transcriptinoal signatures of DRG and spinal neurons from donors with and without a history of pain or opioid
use. We will continue our work to optimize protocols for cutting edge functional and genetic studies in human
nervous system tissue. We will work with other centers to optimize protocols to assess physiological,
transcriptional, and morphological features of human DRG and spinal cord neurons at cellular resolution, and
how these properties are impacted in tissues recovered from patients with a history of pain. Because our donor
population also includes patients with substance use and misuse, and in some cases this overlaps with chronic
pain conditions, we will also characterize similar properties of DRG and spinal cord neurons in patients with and
without a recent history of opioid use. These studies will provide foundational knowledge of human neurons in
the pain neuraxis by mapping electrophysiological features of neurons in the human DRG and spinal cord onto
genetically-defined subpopulations of human DRG or morphological classes of spinal neurons. The study will
also profile tissues derived from donors with and without a history of chronic pain or opioid use/misuse, providing
opportunity for new understanding of the impact of pain and substance use on these neurons in the human pain
neuraxis. Another major deliverable from the present study will be the development of optimized protocols for
key aspects of the proposed analyses, including protocols for RNA sequencing from patch clamped neurons
(Patch-seq) and for the preparation, main...

## Key facts

- **NIH application ID:** 10930011
- **Project number:** 5U19NS130607-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Robert W Gereau
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $488,329
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930011

## Citation

> US National Institutes of Health, RePORTER application 10930011, Functional and genetic characterization of human DRG and spinal cord at single cell resolution (5U19NS130607-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10930011. Licensed CC0.

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