# Anatomic, Physiologic and Transcriptomic Mechanisms of Neuropathic Pain in Human DRG

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $652,350

## Abstract

We have launched a collaborative effort between MD Anderson Cancer Center and University of
Texas at Dallas that uses dorsal root ganglion (DRG) removed from pain phenotyped patients
during neurological surgery. DRGs are taken from thoracic levels during a spine stabilization
surgery and then cut in thirds. One third is saved for immunohistochemistry (IHC) or in situ
hybridization (ISH), one third goes for culturing and electrophysiology, and one third is used for
RNA sequencing. We have developed an extensive dataset with patient pain phenotype
information, DRG neuron electrophysiological characterization and RNA sequencing. In many
cases we have pairs of DRGs from the same patient where the patient had pain in one
dermatome and not in another, allowing for precise case-control analysis. Our electrophysiology
results clearly demonstrate that chronic pain is associated with spontaneous activity (SA) in
DRG nociceptors. This is the first time that this has been demonstrated. Our RNA sequencing
results identify transcriptional changes associated with chronic pain and SA in the DRG that
show indications of sexual dimorphism. In males we find clear signs of immune infiltration and
neuro-immune interactions as well as an increase in expression for some members of the
FOS/JUN transcription factor family. In females we see an upregulation of some G-protein
coupled receptors (GPCRs) and other signs of intrinsic changes in neuronal excitability. These
findings give unique insights into drivers of chronic pain in the DRG in a diverse cohort of
patients with important implications for chronic pain therapeutic development, including the
potential need for sex-specific treatment. Our overarching hypothesis is that SA in human DRG
neurons, which is a critical factor for pain generation in patients, is driven by fundamentally
different mechanisms in male and female patients. We will test this hypothesis using human
DRG samples and a combination of electrophysiology (Aim 1) and RNA-seq (Aim 2). In Aim 3
IHC and ISH along with pharmacological interventions guided by preliminary findings and data
generated during this project will be used to define new potential therapeutic avenues. In sum,
the experiments in this project will give fundamental new insight into mechanisms of chronic
pain that will enable therapeutic and biomarker discovery with the opportunity for an almost
immediate impact on clinical care.

## Key facts

- **NIH application ID:** 10145817
- **Project number:** 5R01NS111929-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Patrick M Dougherty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $652,350
- **Award type:** 5
- **Project period:** 2020-04-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145817

## Citation

> US National Institutes of Health, RePORTER application 10145817, Anatomic, Physiologic and Transcriptomic Mechanisms of Neuropathic Pain in Human DRG (5R01NS111929-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145817. Licensed CC0.

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