# Harnessing T-junction filtering; bidirectional control of sensory neuron impulse traffic

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $451,779

## Abstract

Sensory neurons naturally adapt to ongoing stimulation, but harnessing this inherent plasticity for therapeutic
purposes has not been explored. The recent clinical observation that dorsal root ganglion field stimulation (GFS)
blocks pain, provides a clue that an unrecognized process regulates conduction of impulses through the DRG
since exactly the opposite, i.e. production of pain, would be expected. The paradoxical phenomenon of GFS
analgesia indicates that our current understanding of peripheral neuron signal transmission is fundamentally
insufficient, and that a novel, clinically applicable modality of use-dependent neuronal manipulation awaits
discovery. That is the goal of this proposal. Sensory neurons also convey retrograde impulses from the dorsal
horn to peripheral tissues, where they trigger inflammation and tissue damage, for instance in rheumatoid
arthritis. We will therefore explore bidirectional GFS modulation of both afferent and efferent signal transmission
through the DRG. In three Aims, we will test the overall hypothesis that GFS, by triggering action potentials (APs)
in the somata of sensory neurons, reduces the intrinsic excitability of their T-junction, which reduces bidirectional
propagation of APs through the DRG, and can thereby produce analgesia and block neurogenic inflammation.
In Aim 1, we will first develop a rat model in order to lay the groundwork for mechanistic exploration. GFS
analgesia will be tested in the setting of neuropathy, and osteoarthritis. To test GFS blockade of retrograde
impulses, we will identify GFS effects on joint changes in a model of rheumatoid arthritis. For these experiments,
examination will be by behavioral tests and functional magnetic resonance imaging (fMRI) of the brain, examining
both male and female rats. In Aim 2, to identify the exact neuronal targets of GFS, we will test GFS activation of
sensory neuron somata, and determine which DRG neuronal subtypes are modulated by GFS and at which
component (axon vs. soma) this takes place. Aim 3 will employ electrophysiological approaches to directly
measure the effects of GFS on functional properties of DRG neurons, in order to identify the mechanism of GFS
impulse regulation. Additionally, we will explore the role of CaMKII, and we will compare GFS effects between
the various sensory neuron subpopulations.
Together, our proposed experiments will establish a mechanistic foundation for a novel regulatory process that
governs impulse train transmission in the peripheral nervous system. As molecular and electrical
neuromodulatory therapies move forward in the clinical setting, understanding this new regulatory node will have
direct translational utility for harnessing an inherent impulse regulating system and applying it to control sensory
and peripheral inflammatory disorders.

## Key facts

- **NIH application ID:** 9987745
- **Project number:** 5R01NS103812-04
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Quinn H Hogan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,779
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987745

## Citation

> US National Institutes of Health, RePORTER application 9987745, Harnessing T-junction filtering; bidirectional control of sensory neuron impulse traffic (5R01NS103812-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9987745. Licensed CC0.

---

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