# Intervertebral Disc Degeneration and Cross-Talk with the Nervous System

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $61,260

## Abstract

Intervertebral disc (IVD) degeneration is one of the greatest contributors to low back pain, yet how the IVD can
generate pain remains poorly understood. To date, our knowledge of “cross-talk” between degenerating IVD and
sensory nerves involved in transmitting pain is limited to findings of altered protein and RNA expression in tissues
of the IVD, the spinal cord or dorsal root ganglia (DRG). Recent advances in the imaging of sensory neuron
activation via recording of Ca2+ sensitive fluorescent indicators, together with pre-clinical models of IVD
degeneration, now enable the study of temporal and spatial changes in neuronal function and their “cross-talk”
to changes in the degenerating IVD.
 We propose to evaluate action potential-driven Ca2+ transients and molecular changes in sensory
neurons in a mouse model of injury-induced IVD degeneration. In Specific Aim 1, we will document
temporal changes to pain-related behaviors and sensitivity in Thy1-GCaMP6s mice following puncture of a
lumbar IVD to induce IVD degeneration. These mice carry a transgene for the calcium-sensitive fluorophore,
GCaMP6s, that is expressed in sensory nerves of the DRG. We will also evaluate the presence of neuronal
markers and key ion channels in innervating DRGs, and anatomic changes and nerve fiber infiltration in IVDs,
to test for changes with IVD degeneration as compared to sham controls. This work will document molecular
changes to IVD and DRGs for this model from 6 to 52 weeks of IVD degeneration, and test for relationships
between injured IVD and the innervating lumbar DRGs as a first measure of “cross-talk.” In Specific Aim 2, we
will evaluate action potential-driven Ca2+ transients in lumbar DRG neurons in the IVD degeneration model of
Specific Aim 1. We will record Ca2+ transients in intact DRG of Thy1-GCaMP6s mice in vitro following electric
field stimulation, and measure threshold voltage, 50% maximum (IC50), and numbers of responding DRG
neurons and their nearest neighbor response. DRGs will also be tested before and after incubation with sodium
channel blockers to screen for remodeling of specific ion channel function with periods of IVD degeneration. Our
goal is to identify temporal and spatial changes in DRG function and “cross-talk” with changes of IVD
degeneration. Finally, in Specific Aim 3, we will evaluate sensory stimuli-induced responses in the DRG of
living mice using in vivo fluorescence microscopy. Working with 2-photon confocal microscopy and motion
correction algorithms developed for brain imaging, we will identify the threshold response of DRG neurons in
Thy1-GCaMP6s mice with and without IVD degeneration, following in vivo stimulation of brush, pinch, heat and
cold. Our goal is to test for relationships between in vivo activation of lumbar DRG neurons with behavioral and
sensitivity changes following onset of IVD degeneration. Completion of this study would identify functional
changes to sensory neurons at sites distant to the degenerated IV...

## Key facts

- **NIH application ID:** 10652003
- **Project number:** 3R01AR077678-03S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Lori A. Setton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $61,260
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10652003

## Citation

> US National Institutes of Health, RePORTER application 10652003, Intervertebral Disc Degeneration and Cross-Talk with the Nervous System (3R01AR077678-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10652003. Licensed CC0.

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