# MECHANISMS OF TRPV4-MEDIATED NEUROPATHIC PAIN

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $505,323

## Abstract

SUMMARY
Peripheral neuropathy is one of the most debilitating diseases that significantly impacts patient's quality of life
with recurring pain and imposes staggering economic burdens to our society. Neuropathic pain also represents
a critical unmet medical need because it tends to respond poorly to traditional analgesics and the most
commonly used pain medicines produce serious side effects. Therefore, it is important to identify cells,
molecules, and neural circuits specifically involved at different stages of the pathogenesis of neuropathic pain
to help develop mechanism-based therapies.
Transient receptor potential (TRP) channels are a group of ion channels serving as cellular sensors expressed
by many cell types. TRPV4 is a polymodal sensory transducer integrating a variety of thermal, mechanical and
chemical stimuli. Based on pilot studies, we hypothesize that TRPV4 is required for inflammatory responses
that dynamically catalyze neuropathic pain in the spinal cord. To determine the cellular mechanisms underlying
TRPV4-mediated neuropathic pain we will use a multidisciplinary approach combining generation of cell-
specific TRPV4 mutant mice and bone marrow chimeras, optogenetic activation of TRPV4-expressing cells in
the spinal cord, and neuropathic pain behavioral testing. We will also determine if pharmacological inhibition of
TRPV4 channels and optogenetic inhibition of TRPV4-expressing spinal cells ameliorate peripheral nerve
injury-induced neuropathic pain.
This proposal will establish the cellular basis of TRPV4-dependent immune activation during neuropathic pain
and explore the potential for pharmacological modulation of neuro-inflammation via inhibition of TRPV4
function. Thus, this study advances a unique opportunity to identify unique molecular and cellular targets for
rational design of treatment for neuro-inflammatory diseases resulting in neuropathic pain.

## Key facts

- **NIH application ID:** 9972853
- **Project number:** 5R01AA027065-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Hongzhen Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,323
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972853

## Citation

> US National Institutes of Health, RePORTER application 9972853, MECHANISMS OF TRPV4-MEDIATED NEUROPATHIC PAIN (5R01AA027065-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972853. Licensed CC0.

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