# Mechanisms of Stress-Induced Pain in Veterans

> **NIH VA IK2** · OKLAHOMA CITY VA MEDICAL CENTER · 2021 · —

## Abstract

Many Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OIF/OEF/OND)
veterans experience chronic pain, which is worsened by co-morbid conditions such as post-traumatic stress
disorder (PTSD) and depression. Significantly, there is an unmet clinical need to provide effective treatments
for chronic pain. One hurdle for the development of new therapies is a lack of understanding which
neurotransmitters and brain circuits are responsible for the persistence of chronic pain. Thus, this career
development application will provide the necessary training to develop an independent VA scientist capable of
researching novel brain circuitry responsible for the development of stress-induced chronic pain.
 OBJECTIVES: The objective of this study is to identify the brain circuitry responsible for persistent stress-
induced pain and comorbid behaviors using targeted brain manipulations, including optogenetic techniques.
The overarching hypothesis is that stress induces imbalanced signaling within the limbic brain circuitry
to produce persistent pain hypersensitivity.
 RESEARCH PLAN: This project will utilize two interrelated, independent specific aims. Specific Aim 1 will
test the hypothesis that stress-induced increases corticotropin-releasing factor signaling in the medial
prefrontal cortex leads to persistent visceral and somatic pain-like behaviors. Specific Aim 2 will test the
hypothesis that an imbalance in signaling between limbic brain regions, regulated by corticotropin-releasing
factor and glutamatergic receptors, is responsible for chronic stress-induced hypersensitivity. We will use a
combination of targeted stereotaxic surgeries, cannula implantations, drug microinfusions, and laser
stimulation to modify nociceptive, anxiety-like, and depression-like behaviors in conscious, freely moving rats.
 TRAINING PLAN: Through his mentoring team and consultants, the candidate will receive training on how
to conduct the optogenetic, electrophysiological, and behavioral studies needed to address the research plan.
Additionally, the candidate will take formal courses to promote his professional development, including
responsible conduct of research, statistical analysis, and laboratory management. With formal mentorship to
improve his written and oral communication, the candidate will be able to present the findings of this research
at national and international meetings and publish the results in quality journals.
 ANTICIPATED OUTCOMES: The research in Aim 1 will demonstrate that stress-induces increases in
corticotropin-releasing factor expression within the medial prefrontal cortex leading to enhanced visceral and
somatic sensitivity, which signals through corticotropin-releasing factor receptors in the bed nucleus of the stria
terminalis to produce the behaviors. Specific Aim 2 will show using optogenetic activation that activation of
amygdala terminals or inhibition of medial prefrontal cortex terminals in the bed nucleus of the stria te...

## Key facts

- **NIH application ID:** 10158407
- **Project number:** 5IK2BX003630-05
- **Recipient organization:** OKLAHOMA CITY VA MEDICAL CENTER
- **Principal Investigator:** Anthony C Johnson
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158407

## Citation

> US National Institutes of Health, RePORTER application 10158407, Mechanisms of Stress-Induced Pain in Veterans (5IK2BX003630-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10158407. Licensed CC0.

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