# A preclinical model of peripubertal and adult visceral hypersensitivity

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $406,343

## Abstract

PROJECT SUMMARY/ABSTRACT
Childhood functional abdominal pain (CFAP) is present in about 8% to 38% of 4- to 14-year-old children and
abdominal pain is a prominent symptom in irritable bowel syndrome (IBS), comprising 10% to 15% of the U.S.
population. CFAP adversely affects academic performance and the family socioeconomic conditions. Clinical
studies have noted that female patients report more frequent and greater pain morbidity than male patients.
Clinical studies have identified visceral hypersensitivity (VHS) as an important contributor to visceral pain.
Cellular investigations in affected tissues are required to advance the field, but visceral tissues are seldom
available from human subjects. However, Retrospective studies have identified that severe psychological
stress caused by early life trauma is a risk factor for the development of symptoms CFAP and IBS patients.
Preclinical animal models are essential to identifying the cellular mechanisms of VHS. Preclinical studies in
rodents show that neonatal colon irritation or maternal separation can influence the development of VHS in
later life. However, epigenetic programming is more sensitive to the cellular microenvironment during fetal than
during neonatal development. In this regard, our proposal will advance the field by investigating the cellular
and epigenetic mechanisms by which chronic prenatal stress (CPS) induces sexually dimorphic VHS in adult
and peripubertal offspring. We will test the hypothesis that the development of VHS in response to
chronic prenatal stress is a two-step process: exposure to robust CPS followed by exposure to robust
chronic stress in later life. CPS activates the neuroendocrine axis to trigger 1) fetal programming of such
neurotrophins as brain-derived neurotrophic factor and nerve growth factor, and their receptors trkB and trkA
respectively in the spinal cord; and 2) serotonin synthesis enzymes in the CNS to induce sexually dimorphic
VHS in the offspring. Chronic adult stress (CAS) or chronic peripubertal stress (CPPS) in female offspring
subjected to previous CPS triggers an interaction between spinal cord estrogen and serotonin to epigenetically
upregulate the expression of select neurotrophins to aggravate and prolong VHS.
The specific aims are to investigate: 1) the neurohormonal and cellular mechanisms by which chronic prenatal
stress induces sexually dimorphic visceral hypersensitivity, when subjected to CPPS, and/or 2) the cellular and
epigenetic mechanisms of interactions between the sex steroid hormone estrogen and serotonin in the spinal
cord that aggravate visceral hypersensitivity in female rats subjected to chronic prenatal stress followed by
chronic peripubertal and/or chronic adult stress.

## Key facts

- **NIH application ID:** 9994981
- **Project number:** 5R01DK111819-03
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** John H Winston
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $406,343
- **Award type:** 5
- **Project period:** 2018-09-18 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994981

## Citation

> US National Institutes of Health, RePORTER application 9994981, A preclinical model of peripubertal and adult visceral hypersensitivity (5R01DK111819-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9994981. Licensed CC0.

---

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