# Examination of mu opioid mediated pain vulnerability in combat mild Traumatic Brain Injury

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2022 · —

## Abstract

Nearly 2 million people in the United States sustain traumatic brain injury(TBI) every year and mild TBI(mTBI)
is considered a “signature injury” of those involved in Iraq and Afghanistan conflicts. Pain after such injury
occurs in >50% of the time, worsens clinical course, interferes with community integration, and dramatically
increases the costs of treatment. Despite pain being considered an important public health issue, the
pathophysiology of pain in mTBI is currently unknown, which limits development of novel and effective
treatments. The long-term goal of this research is to determine biological markers for the increased pain
vulnerability after traumatic brain injury that can be used to improve chronic pain prevention and treatments in
our Veterans. The immediate goals of this revised application are to examine the role of opioidergic
transmission and circuitry in the increased pain vulnerability in Veterans who sustained mTBI during combat.
Our central hypothesis is that brain Mu (μ)-opioid receptor (MOR) availability will show regional variability in
Veterans with combat mTBI with and without chronic pain, with most decrease observed in the co-morbid pain
and mTBI group. We will use novel hybrid Positron Emission Tomography and Magnetic Resonance Imaging
(PET-MRI) platform that provides complementary and simultaneous information about the hemodynamic
response and neurotransmitter activation and thus allows direct classification of function of the endogenous
pain control in individuals who has pain and mTBI. This work will allow determination of behavioral,
microstructural, functional and molecular integrity of the opioidergic circuitry and its relationship to clinical pain
behaviors and quality of life. Guided by strong preliminary data the central hypothesis will be tested by
pursuing two specific aims: 1) To examine the complementary impact of mTBI and chronic pain on the
integrity of pain modulatory systems; 2) To distinguish the complementary impact of mTBI and chronic
pain on the capability of pain modulatory systems. This work is significant since it will provide: 1) a
mechanism for pain and enhanced pain vulnerability following mTBI; and 2) better imaging tool to detect pain
after mTBI. Veterans are often prescribed opioids for pain. These drugs have a high potential for abuse and
changes in the endogenous opioid system may contribute to alterations in the rewarding effects of these drugs;
thus mTBI individuals may be particularly vulnerable to exogenous opioids. The current proposal fills an
important gap in understanding how MOR mediated neurotransmission, the primary target of opioid
medications, is affected in pain and mTBI.
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## Key facts

- **NIH application ID:** 10295167
- **Project number:** 5I01CX001652-04
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Irina A Strigo
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295167

## Citation

> US National Institutes of Health, RePORTER application 10295167, Examination of mu opioid mediated pain vulnerability in combat mild Traumatic Brain Injury (5I01CX001652-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10295167. Licensed CC0.

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