# The Role of Mesoaccumbens Dopamine in Pain and Prescription Opioid Addiction

> **NIH VA IK2** · SOUTHEAST LOUISIANA VETERANS HEALTH CARE · 2021 · —

## Abstract

This Veterans Affairs Career Development Award (CDA)-2 will provide support for academic career development
through mentored research and professional skills development in preparation for transition to an academic
research faculty position. Proposed activities will occur under the mentorship of Drs. Nicholas Gilpin, James
Zadina, Scott Edwards, and Tiffany Wills and will foster hypothesis-driven research and independent
investigation. Chronic pain affects >100 million American adults, costing the nation ~$635 billion every year in
medical treatment costs and lost productivity. Due to the high prevalence of chronic pain among Veterans,
treatment of chronic pain is a top priority of the Department of Veteran Affairs (VA), with prescription opioids a
critical first-line treatment for chronic pain patients. However, Veterans treated chronically with opioids for their
chronic pain may be vulnerable to developing opioid addiction and/or using illicit opioids to self-medicate pain
symptoms. Chronic pain and opioid addiction each produce functional abnormalities in the nucleus accumbens
(NAc), including dopamine (DA) deficits, which may be attributable to reduced cell firing of ventral tegmental
area (VTA) DA neurons projecting to the NAc. The NAc mediates the acute rewarding effects of drugs of abuse
via the mesoaccumbens pathway (VTA to NAc) and represents a functional terminus for ascending nociceptive
pathways. However, there remains a gap in our knowledge regarding how chronic pain and limited/escalated
opioid use interact to alter NAc neuronal excitability, drug intake, and pain sensitivity. The purpose of this project
is to examine overlapping brain biochemical mechanisms of chronic pain and opioid dependence that may
contribute to the worsening and potential interdependence of these two disorders. Our central hypothesis is that
chronic pain induces mesolimbic dopaminergic signaling deficits that drive the development of prescription opioid
(i.e., fentanyl) abuse, and fentanyl intake exaggerates pain-like outcomes in rats with chronic inflammatory pain.
Here we propose that I) chronic inflammatory pain increases fentanyl intake, and that fentanyl intake exaggerates
hyperalgesia in rats with chronic inflammatory pain, II) chronic inflammatory pain and fentanyl intake each
increase the intrinsic excitability of NAc neurons and excitatory transmission onto NAc neurons, and III) VTA-
NAc DA circuit activation and/or D2-like receptor agonist treatment each reduce hyperalgesia and escalated
fentanyl intake in rats with chronic inflammatory pain. These hypotheses reflect the order of the aims in this CDA
proposal. To investigate these hypotheses, we propose an innovative experimental strategy that compares the
effects of chronic inflammatory pain states on the electrophysiological properties of NAc neurons and behavioral
deficits (fentanyl intake/motivation, nociception) in animals given long access (LgA; 12 hrs) to fentanyl and short
access (ShA; 1 hr)...

## Key facts

- **NIH application ID:** 10102634
- **Project number:** 5IK2BX004334-02
- **Recipient organization:** SOUTHEAST LOUISIANA VETERANS HEALTH CARE
- **Principal Investigator:** Amanda Rosemary Pahng
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102634

## Citation

> US National Institutes of Health, RePORTER application 10102634, The Role of Mesoaccumbens Dopamine in Pain and Prescription Opioid Addiction (5IK2BX004334-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10102634. Licensed CC0.

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