# Mechanism underlying Nerve Conduction Block by High Frequency (kHz) Biphasic Stimulation

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $234,750

## Abstract

Project Summary
Based on the gate-control theory of pain, traditional spinal cord stimulation (SCS) to treat chronic back/leg pain
utilizes 40-60 Hz stimulation that activates spinal dorsal columns to elicit paresthesia over a patient’s painful
region. This paresthesia-based SCS is only effective for 40-50% of patients with chronic back/leg pain, and the
efficacy gradually reduces over time. A recent advance in SCS employs a high-frequency (10 kHz) biphasic
stimulation waveform (HF10-SCS) at a subthreshold intensity that is paresthesia-free. HF10-SCS is effective
for 80-90% of patients with a better and more sustained long-term (24 months) efficacy than traditional SCS.
The superiority of HF10-SCS over traditional SCS and the paresthesia-free feature indicate that a mechanism
different from the gate-control theory of pain is probably involved in HF10-SCS. Since it is well known that
high-frequency (kHz) biphasic stimulation (HFBS) can block axonal conduction, previous studies have
suggested that HF10-SCS blocks axons in the dorsal roots or axons/neurons in the spinal cord. However,
recent computer modeling and animal studies suggest that paresthesia-free, low intensity HF10-SCS is not
strong enough to either activate or block the axons in the spinal cord. To resolve these conflicting hypotheses,
we need to first understand the mechanisms underlying HFBS block of a single axon. Unfortunately, how
HFBS blocks a single axon is currently unknown. Therefore, in this grant application we will focus on revealing
the mechanisms of HFBS block of single axons. We hypothesize that there are two types of HFBS nerve bock:
1. acute nerve block that occurs only during HFBS; 2. post-stimulation block that occurs during and after
HFBS. Although the acute nerve block requires a supra-threshold HFBS, the post-stimulation nerve block can
be induced by HFBS at a sub-threshold intensity without producing paresthesia. Understanding how HFBS
blocks a single axon is critical for further understanding the mechanisms underlying HF10-SCS suppression of
pain. We propose to combine modeling analysis and animal experiments to reveal the changes in ion
gradients, ion channels, and ion pumps that underlie HFBS axonal block and the recovery of conduction
following the block. We will reveal the biophysics underlying HFBS at the axonal membrane ion channel level
by systematically characterizing, modeling, and validating the axonal response/block induced by HFBS. The
knowledge acquired from our studies is important for understanding neural response to HFBS at a single axon
level either in the central nervous system (spinal cord or brain) or in the peripheral nervous system. Our project
is significant for public health because it provides the basic knowledge not only for understanding the clinically-
proven efficacy of HF10-SCS therapy but also for developing new therapies employing HFBS in the central or
peripheral nervous system.

## Key facts

- **NIH application ID:** 10189730
- **Project number:** 5R01NS109198-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Changfeng Tai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $234,750
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189730

## Citation

> US National Institutes of Health, RePORTER application 10189730, Mechanism underlying Nerve Conduction Block by High Frequency (kHz) Biphasic Stimulation (5R01NS109198-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10189730. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*