# Center for chronic pain and drug abuse

> **NIH NIH P50** · NORTHWESTERN UNIVERSITY · 2020 · $1,805,184

## Abstract

Abstract Overall, Center for Chronic Pain and Drug Abuse:
This is a resubmission of a P50 application, PAR-16-009, to launch a Center for Chronic Pain and Drug
Abuse. Our Center proposal is built on the recognition that opioid addiction and chronic pain engage the same
brain circuitry, the mesolimbic system. Although opiates continue to be prescribed to millions of chronic pain
patients, and chronic pain is a primary contributor to the ongoing opiate epidemic, there is virtually no scientific
knowledge regarding mechanisms that control the interaction between chronic pain and opioid exposure. Our
Center is organized to uncover mechanisms that causally control this interaction, and to aggressively search for
critical molecules, circuits, and biomarkers, and ultimately, novel non-addictive treatment options for chronic
pain. Our overarching hypothesis is that the chronic pain state primes limbic circuitry for opiate
abuse, and also, that associated adaptations depend on the duration and dose of both chronic pain and opioid
exposure. The hypothesis will be rigorously tested using an array of cutting-edge tools, to study the underlying
mechanisms from the scale of genes to molecules, circuits and whole-brain anatomy and function. Patients with
chronic back pain (CBP) are the largest and best characterized group of humans at risk for opioid abuse disorder.
Project 1 will use advanced brain imaging approaches to study brain properties in CBP, and in a rat model of
chronic pain (SNI), for opioid exposure. The human studies will be 1) cross-sectional, comparing brain anatomy
and function between groups; and 2) within-subject, examining brain activity and network properties during
brief opioid withdrawal and re-exposure to placebo, opioid, or dopamine. The study seeks to identify: biomarkers
for opioid use disorder (OUD); brain distortions and cognitive, emotional, and motor changes associated with
opioid exposure; and the role of dopaminergic circuitry in OUD and opioid analgesia. Parallel brain imaging in
rats with chronic pain (SNI) and with morphine exposure (MSA or MCPP) will establish cross-species
correspondences, and interrogate circuitry studied in Projects 2-4. Project 2 will focus on circuits involved in
motivation and addiction (mPFC, NAc, VTA); Project 3 will focus on episodic memory and relapse for opiate
seeking (dorsal hippocampus, dH, interaction with VTA and cortex); Project 4 will focus on genetically defined
single-cell adaptations for the mesolimbic region underlying opioid reinforcement (VTA and its connectivity to
NAc and dH), searching for novel molecular targets to control chronic pain. All animal studies will use the same
model for chronic pain. Projects 2-4 use genetically modified mice; Projects 2, 3 use opto- and chemo-
genetics, and electrophysiology; and Project 4 uses single cell transcriptomics. The rodent behavior core will
generate SNI rodents with MSA or MCPP for all projects. The computational and statistics core will ...

## Key facts

- **NIH application ID:** 9938522
- **Project number:** 5P50DA044121-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Apkar Vania Apkarian
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,805,184
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938522

## Citation

> US National Institutes of Health, RePORTER application 9938522, Center for chronic pain and drug abuse (5P50DA044121-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938522. Licensed CC0.

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