# Prenatal Alcohol Exposure Potentiates Pain via Lifelong Spinal-immune Changes

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $287,162

## Abstract

PROJECT SUMMARY
Exposure to alcohol during gestation can lead to a constellation of mild to severe disabilities that includes
cognitive and behavioral deficits representing a continuum referred to as Fetal Alcohol Spectrum Disorders
(FASD), with a prevalence of ~4.8% in some US regions. A growing body of evidence strongly implicates the
adverse impact of alcohol exposure during central nervous system (CNS) development on cellular and
molecular programing of neuroimmune function. In animal models of prenatal alcohol exposure (PAE),
expression of the brain's immune signaling molecules, the proinflammatory cytokines interleukin-1β (IL-1β),
tumor necrosis factor-alpha (TNF-α) and the chemokine CCL2, are significantly elevated. While evidence of
sensory abnormalities including tactile sensitivity observed in children with FASD are thought to be a result of
psychosocial factors, the underlying cause may include neurological dysfunction. Indeed, animal models of
PAE reveal heightened sensitivity to light touch, a well-known pathological sensory condition mediated by
aberrant neuronal actions in the spinal cord. Clinically, touch hypersensitivity is known as allodynia in chronic
pain patients, and animal models of allodynia show pathological activation of pain neurons occurs in the spinal
cord mediated by IL-1β, TNF-α and CCL2. Glial cells (astrocytes & microglia) are key producers of these
proinflammatory cytokines. Thus, animal models of allodynia and PAE reveal a surprising neuroimmune
overlap. Studies of allodynia in animals show peripheral leukocytes traffic to the spinal cord in response to
CCL2. Notably, leukocytes cross spinal microvascular endothelial cells (MECs) into the CNS by the action of
the β2-adhesion molecule, lymphocyte function associated antigen 1 (LFA-1), and importantly, glial cells control
the healthy barrier function of MECs. Curiously, evidence shows PAE causes structural abnormalities at the
glial CNS-MEC interface. Thus, the long-term goal is to identify spinal MEC & neuroimmune adaptations in
PAE male and female offspring that enhance adult susceptibility to neuropathy. New therapeutic targets to
alleviate aberrant neuroimmune function may be identified. The overall objective will identify the impact PAE
exerts on responses of spinal immune adaptations to minor peripheral nerve & immune challenge in males &
females. Overarching Hypothesis: PAE potentiates spinal and peripheral proinflammatory immune
responses in the nociceptive pathway creating susceptibility for chronic neuropathy from minor insult or
challenge. The Aims of the proposal will: (I) Examine the impact of PAE on cytokine profile and function in
mediating neuropathy from minor insults and immune challenges in adults, (II) Determine the functional
consequences of PAE-induced tight junction defects of the blood-spinal barrier on neuropathy, and (III)
Determine PAE-induced defects of the peripheral immune response underlying susceptibility to neuropathy.
Results wil...

## Key facts

- **NIH application ID:** 9983470
- **Project number:** 5R01AA025967-04
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** ERIN Damita MILLIGAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $287,162
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983470

## Citation

> US National Institutes of Health, RePORTER application 9983470, Prenatal Alcohol Exposure Potentiates Pain via Lifelong Spinal-immune Changes (5R01AA025967-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983470. Licensed CC0.

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