# Adolescent Intermittent Ethanol-Induced Changes in Pain-Related Plasticity Associated with Pain Sensitivity in Adulthood

> **NIH NIH F32** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $72,082

## Abstract

PROJECT SUMMARY
Adolescent alcohol abuse is a significant risk factor for alcohol misuse in adulthood. Of particular concern are
the potential long-term effects on the ability of an individual to appropriately process and respond to pain.
Emerging evidence indicates that adolescent alcohol abuse enhances pain sensitivity and anxiety in adulthood,
and increased pain sensitivity and heightened anxiety may enhance the potential for alcohol misuse later in
life. Recently, a role for a circuit involving the basolateral amygdala (BLA), medial prefrontal cortex (mPFC),
and ventrolateral periaqueductal gray (vlPAG) in pain processing has been described. Within this circuit,
enhanced activity of BLA inputs to the mPFC results in inactivation of mPFC outputs to the vlPAG whereas
inhibition of these inputs results in analgesia. Activity within this circuit is further modulated by dopamine inputs
to the mPFC, which originate in the ventral tegmental area (VTA), leading to a reduction in BLA-driven
feedforward inhibition of vlPAG projecting mPFC neurons. Adolescence is a critical period for development.
Environmental insults occurring during adolescence, such as those caused by repeated episodes of binge-like
alcohol consumption, may disrupt normal development of this circuitry resulting in persistent changes in pain
processing. Interestingly, we have previously demonstrated that adolescent intermittent ethanol (AIE) disrupts
dopamine 1 (D1) receptor function and reduces fast-spiking interneuron excitability in the mPFC of adult
animals, highlighting the susceptibility of the mPFC to AIE-induced changes. The overarching hypothesis of
this proposal is that hyperalgesia in adult rats subjected to AIE-exposure is associated with selective
strengthening of BLA synapses onto parvalbumin positive fast-spiking interneurons (PVINs) in the prelimbic
cortex (PrL). It is further hypothesized that decreased dopamine modulation of PVINs following AIE will
contribute reduced activation of PrL PVINs in response to an inflammatory pain challenge. The proposed
studies will use a combination of projection and cell-type specific labelling, optogenetics, and patch-clamp slice
electrophysiology to assess the effects of AIE-induced changes on pain-related plasticity in BLA-PrL-vlPAG
circuitry as well as AIE-induced alterations in dopamine modulation of mPFC FSINs following a pain challenge.
These experiments will provide novel insight into how alcohol consumption during adolescence contributes to
increased pain sensitivity and anxiety in adulthood. These insights could prove valuable in informing the
development of new treatments designed to target neurocircuitry involved in aberrant pain processing in adults
who consumed alcohol during adolescence.

## Key facts

- **NIH application ID:** 10537245
- **Project number:** 1F32AA030193-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** James Daniel Obray
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $72,082
- **Award type:** 1
- **Project period:** 2022-08-09 → 2023-08-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537245

## Citation

> US National Institutes of Health, RePORTER application 10537245, Adolescent Intermittent Ethanol-Induced Changes in Pain-Related Plasticity Associated with Pain Sensitivity in Adulthood (1F32AA030193-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10537245. Licensed CC0.

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