# Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $106,583

## Abstract

TRPV1 ion channels play a critical role in the increase in sensitivity to pain that occurs in the setting of
inflammation in the cornea and throughout the peripheral nervous system. We address the cellular and
molecular mechanisms by which one of the most important inflammatory mediators, nerve growth factor
(NGF), triggers trafficking of TRPV1 to the plasma membrane. We have previously shown that NGF increases
the number of TRPV1 channels in the plasma membrane of sensory neurons via activation of the enzyme
phosphoinositide 3-kinase (PI3K, Class IA), which phosphorylates the signaling lipid phosphoinositide 
4,5-bisphosphate (PIP2) to make phosphoinositide 3,4,5-trisphosphate (PIP3) (Figure 1A). PIP3 is a ubiquitous
signal for membrane trafficking, and causes TRPV1-laden vesicles to fuse with the plasma membrane via
regulated exocytosis. This enhanced trafficking is facilitated by a direct interaction among the Ankyrin Repeat
Domain (ARD) of TRPV1 and the p85 regulatory subunit of PI3K (Figure 1B). The major preliminary finding
upon which this renewal proposal is based is that the interaction between TRPV1 and PI3K potentiates NGF-stimulated activation of PI3K. This proposal will leverage our preliminary data to investigate the physiology and
mechanism by which this occurs.

## Key facts

- **NIH application ID:** 10414845
- **Project number:** 3R01EY017564-14S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Sharona E Gordon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $106,583
- **Award type:** 3
- **Project period:** 2006-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414845

## Citation

> US National Institutes of Health, RePORTER application 10414845, Inflammatory hyperalgesia due to TRPV1, the pepper spray receptor in the cornea (3R01EY017564-14S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10414845. Licensed CC0.

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