# TNF in Injury and Repair Processes Following Traumatic SCI

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2024 · $497,283

## Abstract

Abstract
Chronic neuropathic pain (CNP) is a maladaptive pathological process that is poorly understood and a condition
for which no effective therapies exist. It is largely recognized that neuroinflammation significantly contributes to
the development of chronic pain, however the mechanisms are not well understood. A unifying mechanism
through which pathological inflammation contributes to the development of chronic pain is by being a key
mediator of neuropathology and maladaptive plasticity in brain regions critical for processing somatosensory
information such as the somatosensory cortex (S1). The overarching hypothesis to be tested in this competitive
renewal is that strategies designed to mitigate pathological neuroinflammation will be therapeutic for spinal cord
injury (SCI)-Pain by promoting neurorepair and reducing maladaptive supraspinal plasticity. The studies
proposed in this application are based upon extensive published and preliminary data demonstrating diverging
roles for TNFR (TNFR1 and TNFR2) signaling and sex differences in the development and resolution of CNP in
SCI and peripheral nerve injury (CCI) models. The overarching goals of our competitive renewal are to better
understand mechanisms of CNP and to develop therapies that are effective in both women and men.
 The lack of understanding of neuron-immune cell interactions that lead to the development or resolution
of chronic pain is the overarching scientific premise to this application. Our scientific premise and hypotheses
will be tested in the following Specific Aims.
Specific Aim1: Interrogate the mechanisms through which TNFR2 signaling mitigates neuroinflammation in
CNP in males and females.
Specific Aim 2: Interrogate the divergent roles for TNFR signaling in the development and resolution of CNP
and maladaptive plasticity in males and females.
Specific Aim 3: Interrogate the intersection between TNFR1 and ERβ in females and mechanisms whereby
inhibiting ERβ in females renders them “male-like” with respect to therapies for CNP.

## Key facts

- **NIH application ID:** 10744388
- **Project number:** 2R01NS051709-17A1
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** John Roland Bethea
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $497,283
- **Award type:** 2
- **Project period:** 2005-04-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10744388

## Citation

> US National Institutes of Health, RePORTER application 10744388, TNF in Injury and Repair Processes Following Traumatic SCI (2R01NS051709-17A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10744388. Licensed CC0.

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