# Validation of blocking TSP4/Cava2d1 interaction as a new target for neuropathic pain

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $96,630

## Abstract

Project Summary/Abstract
 Validation of a novel pain target is a critical step toward the development of new
nonaddictive, therapeutic agents for chronic pain management, which is an urgent unmet
medical need to be tackled by NIH's Helping to End Addiction Long-term (HEAL) initiative.
We recently discovered that nerve injury induced concurrent upregulation of the calcium
channel alpha-2-delta-1 subunit (CaV21) and thrombospondin-4 (TSP4) proteins in sensory
and spinal cord neurons that contributes to neuropathic pain development by inducing
aberrant excitatory synapse formation and sensitization of neurotransmission in spinal cord.
We have identified a target side in the TSP4 that plays a critical role in mediating these
pathological changes upon interaction with the CaV21 protein. To validate this novel target
site for development of nonaddictive pain medications, we plan to use multidisciplinary
approaches, involving three independent laboratories, to investigate if blocking and genetic
deletion of the target site can block/prevent (Aim 1) pain state development; (Aim 2) aberrant
excitatory synapse formation; (Am 3) spinal cord neuron sensitization after injury in two
neuropathic pain models. Successful completion of this project will provide important
information for further development of specific therapeutic medications for neuropathic pain
management as inspired and supported by the HEAL initiative.

## Key facts

- **NIH application ID:** 10670457
- **Project number:** 3R01DE029202-01S4
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** ZHIGANG David LUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $96,630
- **Award type:** 3
- **Project period:** 2019-09-24 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10670457

## Citation

> US National Institutes of Health, RePORTER application 10670457, Validation of blocking TSP4/Cava2d1 interaction as a new target for neuropathic pain (3R01DE029202-01S4). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10670457. Licensed CC0.

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