# Novel mechanisms regulating protein interaction and pain

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $528,135

## Abstract

Project Abstract
As much as 20% of the population will suffer from chronic pain lasting for more than 6 months. Chronic pain
and its underlying pathophysiology, can result in depression and other debilitating neurological effects and
although there are effective treatments for acute pain chronic pain is resistant to most current treatments
requiring the development of novel therapeutics that target molecular events underlying these pain states.
Neuropathic and persistent post-surgical pain occurs, at least in part, due to long lasting changes in the
function of excitatory synaptic transmission in the spinal dorsal horn resulting in enhanced pain signaling
(hyperalgesia) and innocuous stimuli evoking pain (allodynia). These synaptic events share many features of
neuronal plasticity that has been studied in higher CNS areas. Many of these changes are NMDAR dependent
resulting in increased synaptic strength. One mechanism that has emerged underlying these changes in
synaptic function is the potentiation of NMDAR function by a direct molecular interaction with the EphB
receptor tyrosine kinase. Building on our published work, we will test the hypothesis that an EphB-NMDAR
interaction is responsible for the development of a chronic pain state by directing NMDARs to synapses by
expressing wild type or mutant EphB2 receptors in vitro and in mice. To test this hypothesis, we will determine
the mechanism mediating the EphB-NDMAR interaction, characterize molecules and other tools to disrupt this
interaction, and determine whether preventing the EphB-NMDAR interaction will alleviate chronic pain. To
address these questions we will undertake three specific aims: 1. Determine the domain on the NMDAR
responsible for the EphB-NMDAR interaction. 2. Test the hypothesis that VLK directs phosphorylation
of Y504 on EphB2. 3. Determine the functional significance of VLK in pain plasticity. Collectively these
aims will create a new knowledge that will provide a deeper understanding of the role of EphB-NMDAR
interaction in pain and enable progress toward understanding the basic mechanisms behind chronic pain
states.

## Key facts

- **NIH application ID:** 9914746
- **Project number:** 1R01NS115441-01
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Matthew B Dalva
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $528,135
- **Award type:** 1
- **Project period:** 2019-12-15 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914746

## Citation

> US National Institutes of Health, RePORTER application 9914746, Novel mechanisms regulating protein interaction and pain (1R01NS115441-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9914746. Licensed CC0.

---

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