# Optimized Electrical Block of Peripheral Nerves

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $489,172

## Abstract

Electrical block of neural conduction has myriad potential clinical applications including treatment of pain and
autonomic dysfunction such as heart failure, diabetes and inflammation. However, these therapeutic targets
require block of small diameter myelinated Ad- and B-fibers and unmyelinated C-fibers, while the majority of prior
studies of block were on block of large diameter myelinated Aa-fibers. The continued development of nerve block
and its clinical translation are limited by: (1) the high energy required for conduction block, especially for the
small diameter nerve fibers most relevant for bioelectronic therapies, (2) the strong excitatory response that
occurs at the onset of blocking signals, which is likely to be exacerbated by the high block thresholds of small
diameter axons, and (3) the lack of control over which specific nerve fibers are blocked, such that blocking small
diameter axons also results in block of larger diameter axons. We propose rigorous engineering design to
optimize the performance of nerve block waveforms and electrodes and in vivo testing of their performance in
both small and large animals. Aim 1 is to optimize simultaneously the waveform and electrode geometry to meet
each of three distinct performance criteria: minimize energy required for block, minimize onset response
associated with the initiation of block, and enable selective block of small diameter axons (myelinated Ad- or B-
fibers or unmyelinated C-fibers) while preserving conduction in large diameter Aa-fibers. We will combine
validated computational models with engineering optimization via a particle swarm algorithm to design new
waveform shapes and electrode geometries to achieve our performance metrics and thereby greatly increase
the utility of nerve conduction block. In Aim 2, we will measure the responses of different types of nerve fibers
(A-, B-, and C-fibers) in both the vagus nerve and the sciatic nerve of anesthetized rats to compare the
performance of optimized block waveforms and electrode geometries to conventional waveform shapes
(sinusoids, rectangular pulses) and electrode geometries (bipolar, tripolar) used for block of nerve fiber
conduction. In Aim 3 we will measure both nerve fiber responses and physiological responses, including
electromyograms and changes in heart rate, to block of the pig vagus nerve to quantify performance, including
energy, onset response, and selectivity, in a large, multi-fascicular nerve that represents well human nerves.
The outcomes will be novel waveforms and electrode geometries that overcome the performance limitations of
current approaches to conduction block including the high energy requirements, the strong excitatory onset
response, and the lack of control over which specific nerve fibers are blocked. These enhanced capabilities will
advance electrical nerve block as an experimental tool and provide technologies to enable the continued
translation of new bioelectronic therapies.

## Key facts

- **NIH application ID:** 10763873
- **Project number:** 5R01NS126376-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Warren M. Grill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $489,172
- **Award type:** 5
- **Project period:** 2023-01-15 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763873

## Citation

> US National Institutes of Health, RePORTER application 10763873, Optimized Electrical Block of Peripheral Nerves (5R01NS126376-02). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10763873. Licensed CC0.

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