# Central Mechanisms Modulating Visceral Sensitivity

> **NIH VA I01** · OKLAHOMA CITY VA MEDICAL CENTER · 2021 · —

## Abstract

OBJECTIVES OF THE PROJECT: This resubmission of a VA Merit grant renewal continuously funded
since 2005 focusing on understanding the basic mechanisms that underlie chronic pain and translating those
findings into new therapeutic options for both male and female Veterans. This is important as current
therapeutic approaches for treating our Veterans with chronic pain are largely ineffective due to a paucity of
understanding of the mechanisms leading to chronic pain.
RESEARCH PLAN & METHODOLOGY: This renewal application will build upon the novel findings from
the parent grant and also takes advantage of cutting edge discovery approaches to delineate neural pathways
and molecular mechanisms leading to stress-induced chronic pain. There is evidence of increased pain
reporting in female veterans, thus specific Aim 1 will utilize state of the art approaches to test the hypothesis
that sexually dimorphic epigenetic dysregulation in the central nucleus of the amygdala (CeA) underlies gene
expression changes mediating the persistent effects of stress on visceral nociceptive processing. Under Specific
Aim 2 we will take advantage of clinical evidence suggesting that chronic pain in patients can be reduced by
psychological therapies such as biofeedback, relaxation training and yoga; however, the mechanisms by which
such psychotherapies improve clinical pain are unknown. We will build upon our preliminary data showing the
therapeutic potential of environmental enrichment to reverse stress-induced visceral pain by restoring
corticotropin-releasing hormone (CRH), GR and mineralocorticoid receptor (MR) expression in the CeA. This
aim will also investigate whether epigenetic mechanisms in the CeA underlie the effects of EE on chronic
stress-induced visceral pain.
ANTICIPATED OUTCOMES: In this application, we propose an approach that offers a novel way of
thinking about chronic pain by using state of the art epigenetic techniques combined with classical behavioral
outcome measures to identify mechanisms that will enhance our basic understanding of chronic pain. Under
Specific Aim 1 we anticipate that there are unique central mechanisms driving female vulnerability for pain. We
expect to show that heightened pain following chronic adult stress is modulated through epigenetically
mediated mechanisms within the CeA, and that there will be significant differences between males and females.
Under Specific Aim 2 we anticipate reversing the abnormal molecular events occurring within the CeA in
response to chronic stress using environmental enrichment and investigate the importance of histone
modifications to mediate the effects of environmental enrichment.
RELEVANCE TO VETERANS HEALTH: Taken together the work proposed in this VA Merit grant will
substantially advance our understanding of the neural and molecular level events responsible for chronic pain
and taken together with our previous data provide a unifying central hypothesis for how stress leads to chronic
pain. ...

## Key facts

- **NIH application ID:** 10155425
- **Project number:** 5I01BX002188-07
- **Recipient organization:** OKLAHOMA CITY VA MEDICAL CENTER
- **Principal Investigator:** Courtney Wayne Houchen
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155425

## Citation

> US National Institutes of Health, RePORTER application 10155425, Central Mechanisms Modulating Visceral Sensitivity (5I01BX002188-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10155425. Licensed CC0.

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