# Systematic characterization of inhibitory subpopulations activated by spinal cord stimulation using a targeted strategy

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $423,500

## Abstract

Project Summary
Spinal cord stimulation is an opioid-sparing neuromodulation therapy commonly used for the
treatment of intractable chronic pain of the back and limbs. There is a substantial need to
understand the fundamental biological mechanisms of SCS in order to improve clinical delivery
and outcomes. It has proven challenging to characterize the inhibitory populations engaged by
SCS, as electrophysiological recordings are vulnerable to interference from stimulation artifacts
and only sample a sparse subset of active neurons. Immediate-early gene (c-fos) expression
studies have been equivocal and did not distinguish excitatory and inhibitory populations.
Therefore, it remains unknown whether SCS drives activation of distinct inhibitory subpopulations
in a stimulation amplitude- and frequency-dependent manner. An innovative mouse model will be
used to tag activated neurons during prolonged SCS delivered via chronically implanted
miniaturized bipolar electrodes. A wide range of clinically-relevant SCS waveforms will be
employed, and activated neurons will be molecularly phenotyped and visualized in situ via
multiplexed RNA hybridization. Probes against specific molecular markers will be used to classify
neurons in distinct inhibitory clusters, and statistical models will developed to characterize effects
of stimulation parameters on neuronal clusters. This project will spatially and molecularly identify
the inhibitory subpopulations activated by the full spectrum of clinically-relevant SCS waveforms.
This information will dramatically improve the ability to design waveforms targeting specific spinal
cord circuits, and have direct translational relevance, opening the door to rational implementation
of SCS for distinct clinical pathologies.

## Key facts

- **NIH application ID:** 10571637
- **Project number:** 1R21NS130291-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Andrei D Sdrulla
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,500
- **Award type:** 1
- **Project period:** 2022-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10571637

## Citation

> US National Institutes of Health, RePORTER application 10571637, Systematic characterization of inhibitory subpopulations activated by spinal cord stimulation using a targeted strategy (1R21NS130291-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10571637. Licensed CC0.

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