# Peripheral Neuronal and Non-neuronal Mechanisms of Fabry Disease Pain

> **NIH NIH F31** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Fabry Disease (FD) is one of the most common lysosomal storage diseases and causes devastating pain in
patients starting at a young age. While clinical literature has shown that patients with FD have mechanically-
evoked pain, ongoing pain, and peripheral nerve damage, it is unclear how FD pain is mediated in the
peripheral nervous system (PNS). My proposal will investigate how PNS cellular mechanisms mediate FD pain
using the FD rat model, which recapitulates the pain phenotypes seen in patients. Abnormal ion channel
activity on neurons is linked to peripherally mediated pain in many diseases. However, recent evidence has
shown that pain-associated ion channels in neurons are also expressed in non-neuronal cells. Decreasing
Schwann cell (SC) ion channel activity can ameliorate mechanically-evoked pain behaviorally in other pain
conditions. It has been hypothesized that algogens released from SCs are influencing mechanically-evoked
pain. We have shown that mechanically-evoked pain in FD depends on the activity of the ion channel Transient
Receptor Potential Ankyrin 1 (TRPA1) in the PNS. In my proposal, I will determine if TRPA1 also mediates
ongoing pain through PNS activity of FD rats. I will also determine if algogens released from FD SCs activate
or sensitize neurons to mechanical force, and if SC TRPA1 drives mechanically-evoked pain in FD. I
hypothesize that increased activity of TRPA1 in both Schwann cells and neurons is critical for
maintaining chronic pain phenotypes in the FD rat. In Aim 1, I will determine if the FD rat has behavioral
ongoing pain and aberrant peripheral nerve activity that is dependent on TRPA1. I will use a battery of ongoing
pain behavior techniques and determine if TRPA1 inhibition alleviates this pain (Aim 1A). I will then determine
whether peripheral TRPA1 is required for spontaneous axonal activity in the FD rat by using ex vivo teased
fiber recordings (Aim 1B). In Aim 2, I will investigate the role that SCs play in TRPA1-dependent mechanical
hypersensitivity in FD. First, I will determine if sensory neurons are activated or sensitized by algogens
released from FD SCs, and if neuronal TRPA1 is required for this activation (Aim 2A). Next, I will determine if
algogens from FD SCs sensitize neurons to mechanical stimulation using patch-clamp recordings, and if this
depends on neuronal TRPA1 activity (Aim 2B). Finally, I will determine if viral inhibition of SC TRPA1 can
alleviate FD mechanical hypersensitivity through a battery of pain behavior assays (Aim 2C). My proposal will
provide a basis for how Schwann cells mediate chronic pain and will advance our understanding of
Fabry Disease pain.

## Key facts

- **NIH application ID:** 10387377
- **Project number:** 1F31NS122380-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Tyler B. Waltz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387377

## Citation

> US National Institutes of Health, RePORTER application 10387377, Peripheral Neuronal and Non-neuronal Mechanisms of Fabry Disease Pain (1F31NS122380-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10387377. Licensed CC0.

---

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