# Unraveling the transcriptional response of sensory neurons to spinal cord injury at the single cell level

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $433,125

## Abstract

ABSTRACT
 Spinal cord injury (SCI) damages long projecting axons leading to loss of sensory and motor function.
Permanent disability results because injured axons in the spinal cord fail to regenerate, leaving them
disconnected from their targets. There are currently no therapies to restore mobility and sensation following
SCI. Therefore, a better understanding of the cellular and molecular mechanisms that compromise axon
regeneration after SCI is needed to develop new strategies to restore function.
 Sensory dysfunctions and neuropathic pain are often the consequences of SCI. Sensory neurons are
located in dorsal root ganglia (DRG) and are pseudo unipolar: in addition to a peripherally projecting axon
that receive sensory information, they extend a centrally-projecting axon into the spinal cord that transmit this
information to the brain. Whereas injury to the peripheral axon elicits a regenerative response, injury to the
central axon fails to do so. Regeneration failure has been attributed in part to the weak regeneration-
associated gene (RAGs) response upon injury. However, previous studies have assessed changes in gene
expression using whole lumbar DRG after SCI, but only proprioceptors and low threshold mechanoreceptors
(LTMRs) ascend the spinal cord and are injured after thoracic or cervical SCI. Furthermore, neurons are
outnumbered by glial cells and other cell types within DRG, which may also contribute to the failed
regeneration after SCI. Because of this remarkable heterogeneity in cell types, analyses of the neuronal and
non-neuronal responses to injury has remained a challenge. Therefore, whether and how sensory neurons
and the surrounding cells respond to SCI remains unclear. Based on our preliminary studies, we have now
reason to believe that SCI results in gene expression changes in proprioceptors and LTMRs that have little
overlap with those of peripheral injury, potentially constituting a roadblock for regeneration. The indirect
effects of SCI on the non-neuronal cellular environment in the DRG also remain largely unexplored. Using
transcriptional analysis at the single cell resolution, we identified a pro-regenerative role of the glial cells that
envelop the neuronal soma, known as satellite glial cells. Our goal is now to use single cell transcriptional
approaches to unravel how distinct sensory neuron subtypes and the surrounding non-neuronal cells respond
to SCI. These approaches may lead to new therapeutic targets to promote axon regeneration and treat
neuropathic pain after SCI.

## Key facts

- **NIH application ID:** 10072668
- **Project number:** 1R21NS115492-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Valeria Cavalli
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $433,125
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072668

## Citation

> US National Institutes of Health, RePORTER application 10072668, Unraveling the transcriptional response of sensory neurons to spinal cord injury at the single cell level (1R21NS115492-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072668. Licensed CC0.

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