The goal of this study is to elucidate the mechanisms of action of dorsal root ganglion stimulation (DRGS) for chronic pain. Chronic pain affects approximately 100 million Americans, and accounts for more than 600 billion dollars in healthcare costs each year. DRGS is an FDA-approved neurostimulation therapy for chronic pain that is refractory to conventional medical management. Although some patients receive sufficient pain relief in response to DRGS, clinical outcomes are often inconsistent. This variation in pain relief across patients may be due to poor understanding of the physiological mechanisms governing stimulation-induced pain relief. Therefore, we seek to uncover these mechanisms to ultimately optimize DRGS and improve clinical outcomes. This study is driven by previous computer modeling results from our lab showing that within stimulation parameter ranges used clinically, DRGS is likely driving the activity of large myelinated sensory neurons. In this proposed study, we will further investigate these mechanisms using computational models to determine sources of interpatient variability in DRGS outcomes. Furthermore, we will validate these models using clinical electrophysiological data, and inform the cellular anatomy of our models using histological data. We hypothesize that electrode location will be the largest source of variability in DRGS outcomes, and that positive DRGS outcomes will predict predominant activation of large myelinated sensory neurons. This project aims to characterize the mechanisms of action of DRGS to improve the implementation and outcomes of the therapy, and the models resulting from this project could be used to systematically design and test novel stimulation technologies (e.g. electrode and waveform design).

Public Health Relevance

The goal of this project is to elucidate the mechanisms of action of dorsal root ganglion stimulation (DRGS) for chronic pain. We will construct patient-specific models of DRGS and validate the models against clinical electrophysiology data to determine the neurophysiological mechanisms of stimulation-induced pain relief. Understanding the mechanisms of DRGS may lead to optimizing the therapy to improve patient outcomes, and these models could be used to systematically design and test novel stimulation technologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS113407-01A1
Application #
9989976
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Oshinsky, Michael L
Project Start
2020-09-01
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Engineering (All Types)
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109