The central goal of this project is to advance the therapeutic applications and the potential for using ionic direct current to interact with the nervous system. Direct current (DC) compared to biphasic charge balanced pulses normally used by neural prostheses to interface to the nervous system, can more naturally control neural activity. Unlike biphasic current pulses used to excite neurons, DC can excite, inhibit, and modulate sensitivity of neurons. While DC can be used for short durations to interact with the nervous system, chronic use of this stimulation paradigm for implantable prosthetic applications has not been possible due to the DC?s inherent violation of the charge injection safety constraints at the metal electrode interfaces. New technology, safe direct current stimulation (SDCS) overcomes these constraints and opens an additional avenue for research into exciting possibilities of using DC to interface to the nervous system. We will optimize the use of ionic DC to improve the performance of chronic pain suppression. Chronic pain suppression requires inhibiting pain carrying neurons from conducting action potentials. We obtained preliminary data in an anesthetized rat model showing that safe DC neural block at the sciatic nerve could suppress pain signals from propagating to the spinal cord, but allow normal propagation of sensation and muscle movement. Here we propose to understand the mechanism behind safe DC modulation of pain signals through anesthetized mouse and rat experiments. We will conduct the behavioral experiments to understand the effectiveness of this technology for addressing chronic pain in an awake animal. We will also conduct histological studies to investigate the biological impact of the therapy. Finally, we will advance the SDCS technology by identifying and solving the key technical challenges with a miniaturized and implantable SDCS.
Aim 1. Examine the mechanism of the iDC effect on suppression of nociceptive pain.
Aim 2. Examine the effects and underlying mechanisms of iDC on neuropathic pain signals.
Aim 3. Behavioral experiments to study iDC for inhibition of neuropathic pain.
Aim 4. Implantable SDCS technology development.

Public Health Relevance

Neural prostheses are able to deliver reliable and efficient functional excitation of the nervous system to enable technology such as cochlear implants, retinal implants, pacemakers, spinal cord stimulators, and deep brain stimulators. Conversely, suppression of the nervous system is not easily achieved. The central goal of this project is to advance the technology toward achieving efficient suppression of the nervous system and to improve the application of neural prostheses for the treatment of chronic pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS110893-01A1
Application #
9885600
Study Section
Somatosensory and Pain Systems Study Section (SPS)
Program Officer
Oshinsky, Michael L
Project Start
2020-04-15
Project End
2024-04-14
Budget Start
2020-04-15
Budget End
2021-04-14
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205