# Neurobiological Consequences of Long-Term Opioid Therapy in the Brain and Spinal Cord

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $636,122

## Abstract

Project Summary/Abstract
Opioids are potent analgesics, and despite considerable side effects and risks for overdose and addiction,
many patients continue long-term opioid therapy. Based on prior NIDA-funded research (DA040154), we have
published initial data from brain functional MRI (fMRI) studies that demonstrate significantly altered brain
response to reward in patients on long-term opioid therapy. Our preliminary data from innovative high-
resolution fMRI of the cervical spinal cord revealed disrupted resting-state functional connectivity of the spinal
cord dorsal horns in the same patients. Thus, long-term opioid therapy has neurobiological consequences on
responses to stimuli and neural circuitry at both brain and spinal cord levels. Due to the opioid epidemic, there
is an urgent need to understand neurobiological consequences of opioids, as stated in Goal 1 of the NIDA
Strategic Plan, to aid patients and clinicians in opioid cessation strategies, and to inform novel ways to reverse
neurobiological consequences of long-term opioid use. Our overall objective in this project is to characterize
neurobiological consequences of long-term opioid therapy on brain reward systems and spinal cord circuitry, 2
interacting focal points in the central nervous system. Our central hypothesis is that in long-term opioid
therapy patients, opioid use transiently improves responses to stimuli, while disrupting functional
connectivity of neural circuits within the brain and spinal cord. To test this hypothesis, we will collect and
analyze data from task-based and resting-state fMRI of the brain, and high-resolution fMRI of the spinal cord in
long-term opioid users (ie, > 90 days duration, homogeneous sample of female patients with fibromyalgia, as
included in our preliminary data). We will evaluate brain and spinal cord fMRI-based activity in opioid patients
(N = 40) by using a novel within-subject design to compare activity in active vs non-active opioid states (timed
to opioid administration and blood opioid level) to activity in opioid-naïve patients (N = 40) and healthy controls
(N = 40). In Aim 1, we will characterize neurobiological consequences of long-term opioid therapy on brain
fMRI-based response to reward probability, and on resting-state fMRI-based functional connectivity of a key
brain reward circuit. In Aim 2, we will characterize neurobiological consequences of long-term opioid therapy
on spinal cord fMRI-based response to noxious heat stimuli, and on resting-state fMRI-based functional
connectivity between dorsal horns. To identify neurobiological targets related to clinical endpoints of opioid
use/misuse and addiction behavior, exploratory analyses will be integrated across aims to assess relationships
between brain and spinal cord fMRI-based endpoints, and cognitive-affective and clinical measures. Together,
the proposed project will provide important and rigorous opioid dose-timed evidence of neurobiological
consequences of long-term opioi...

## Key facts

- **NIH application ID:** 10861817
- **Project number:** 5R01DA055850-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Katherine Theresa Martucci
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $636,122
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861817

## Citation

> US National Institutes of Health, RePORTER application 10861817, Neurobiological Consequences of Long-Term Opioid Therapy in the Brain and Spinal Cord (5R01DA055850-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10861817. Licensed CC0.

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