# Mechanistic underpinnings of chronic low back pain

> **NIH NIH U19** · UNIVERSITY OF TEXAS DALLAS · 2022 · $652,365

## Abstract

Chronic low back pain (CLBP) is the leading cause of disability worldwide and current treatments are mostly
ineffective. The proposed project aims to use RNA-seq techniques with cellular resolution on nerve, joint, muscle,
and fascia tissues from thoroughly-phenotyped individuals with CLBP undergoing spine surgery to gain new
insight into CLBP. Our central hypothesis is that transcriptional changes in nerves and pathological tissues drive
human CLBP. We will test this hypothesis by applying single cell RNA-seq to tissue samples of thoroughly
characterized patients with CLBP undergoing surgery. In our first aim we will apply single nucleus and bulk RNA-
seq to the peripheral and neural tissues outlined above. We hypothesize that peripheral and neural tissues from
patients with CLBP will display shifts in cell types and ligands that give insight into distinct mechanisms of CLBP.
In our second aim we will apply our computational interactome model to our RNA-seq data to identify ligand-
receptor interactions between cells/tissues associated with CLBP and neuronal transcriptomes. We will
associate nociceptor phenotypes assembled from our collective DRG datasets from organ donors and chronic
pain patients to create interactome profiles from CLBP tissues, and associate these interactomes to pain
phenotypes. Finally, in our third aim we will conduct in vitro pharmacology studies on human DRG neurons from
organ donors to understand how putative pain mediators act on nociceptors. The project will lead to a new
understanding of CLBP, and elucidate pain phenotype-specific therapeutic opportunities based entirely on
human molecular neuroscience. The research project will serve as an example of how platforms that are based
entirely on the use of human samples and tissues can be developed for discovery, target identification and
clinical validation for other pain disorders.

## Key facts

- **NIH application ID:** 10593659
- **Project number:** 1U19NS130608-01
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Michele Curatolo
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $652,365
- **Award type:** 1
- **Project period:** 2022-09-19 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10593659

## Citation

> US National Institutes of Health, RePORTER application 10593659, Mechanistic underpinnings of chronic low back pain (1U19NS130608-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10593659. Licensed CC0.

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