# Investigating the Neural Circuits of Spinal Cord Stimulation

> **NIH NIH K08** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $21,600

## Abstract

Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of refractory neuropathic
pain. It is believed that SCS mediates pain relief by electrical stimulation of Aβ fibers (Aβ-ES), however a detailed
understanding of its biological basis is lacking, particularly concerning how it engages spinal cord nociceptive
pathways. The long-term goals of this proposal are to delineate the spinal mechanisms of SCS-induced
analgesia in an effort to optimize its clinical implementation for the treatment of chronic pain. The overall objective
of the present application is to dissect the influence of Aβ-ES on defined neuronal microcircuits, and test the role
of a critical candidate subpopulation for the analgesic effects of Aβ-ES. The central hypothesis is that Aβ-ES
achieves analgesia by inducing dynamic changes in specific populations of spinal cord neurons residing in the
superficial dorsal horn (SDH). This hypothesis will be tested by pursuing three specific aims: 1) Determine the
extent to which a conditioning train of dorsal root Aβ-ES modulates high-threshold (C-fiber) evoked activity of
excitatory and inhibitory neurons in the SDH in an en bloc spinal cord preparation from naïve and nerve-injured
mice. 2) Use in vivo imaging to determine the extent to which a conditioning train of dorsal column Aβ-ES
attenuates peripherally evoked activity of excitatory and inhibitory neurons, in the superficial dorsal horn, in naïve
and nerve-injured mice. 3) Determine the role of somatostatin expressing neurons in dorsal column Aβ-ES
mediated analgesia. The proposed approach takes advantage of state-of-the-art ex vivo and in vivo two-photon
imaging coupled with optogenetic approaches to delineate the effects of Aβ-ES on defined neuronal populations
in real time. The proposed research is significant because a detailed understanding of how Aβ-ES engages the
dorsal horn will provide a direct biological target for enhancements to SCS therapies with a sound mechanistic
basis. This work will thus have direct translational relevance, as it may help optimize spinal cord stimulation
programs and improve patient outcomes.
Dr. Andrei Sdrulla is a MD/PhD clinician-scientist whose career goals are to become a successful, independently
funded pain researcher and a clinical leader in the field of neuromodulation. Dr. Sdrulla will work closely with his
comprehensive mentorship team to develop expertise in quantitative imaging of neuronal populations, in vivo
imaging, mouse models of chronic pain and optogenetic manipulation of neuronal populations in behaving
animals. This training will be accomplished primarily via performing experiments under supervision from his
mentors, as well as structured training consisting of didactics, face-to-face instruction and seminars. Dr. Sdrulla
will be conducting his research within Oregon Health & Science University’s Department of Anesthesiology
Laboratories, a uniquely collaborative environment constructed on a foundat...

## Key facts

- **NIH application ID:** 10263824
- **Project number:** 3K08NS099503-03S1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Andrei D Sdrulla
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $21,600
- **Award type:** 3
- **Project period:** 2018-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263824

## Citation

> US National Institutes of Health, RePORTER application 10263824, Investigating the Neural Circuits of Spinal Cord Stimulation (3K08NS099503-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10263824. Licensed CC0.

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