February 4, 2020

Neuroscientist Alana Conti explores anti-inflammatory to help veterans using opioid-based medications after brain injuries

Veterans who have sustained a traumatic brain injury are more likely to receive treatment with opioid-based medications and engage in higher-risk opioid use patterns, but no studies have explored the long-term consequences of such treatment on TBI-related outcomes.

Alana Conti
Alana Conti, Ph.D.

Wayne State University neuroscientist and Associate Professor of Neurosurgery Alana Conti, Ph.D., will change that with a new four-year award for $1,186,779 from the U.S. Department of Veterans Affairs Rehabilitation Research and Development Service.

“Active duty and reserve service members are at an increased risk of sustaining a traumatic brain injury compared to civilians due to combat-related activities,” Dr. Conti said. “Therefore, the overall goal of this work is to develop useful rehabilitative strategies for reducing adverse functional outcomes related to addiction and pain in the delayed post-TBI period that are exacerbated with opioid-based pain management. This proposal seeks to accomplish this by identifying alterations in oxidative stress and inflammatory mediators and testing translationally-relevant therapies to reduce the burden of TBI-related deficits and improve the quality of life for veterans suffering from TBI.”

The project is a pre-clinical model driven by collaborator Kelly Bosse, Ph.D., a research associate and health science specialist at the John D. Dingell VA Medical Center, and the principal investigator on a related SPiRE (Small Projects in Rehabilitation Effectiveness) grant from the VA as well.

Professor of Psychiatry and Behavioral Neurosciences Cynthia Arfken, Ph.D., and Associate Professor of Psychology George Borszcz, Ph.D., are also part of the team.

Of the more than 300,000 service men and women that have sustained traumatic brain injuries due to recent conflicts, 70% to 80% are treated for pain, Dr. Conti said.

While the exact mechanisms underlying a synergy between TBI and early opioid exposure are unknown, recent data indicates that morphine -- the typical opioid therapeutic -- leads to activation of reactive oxidative species and pro-inflammatory mediators. Morphine given post-TBI could enhance or extend the induction of these systems, worsening pathological pain and contributing to addiction vulnerability, she said.

She hypothesizes that morphine exposure following TBI will heighten injury-induced alterations, but should be reversed through neurotherapeutic intervention with a glial attenuator called ibudilast. 

A glial cell provides support and protection for neurons in the central and peripheral nervous systems. Ibudilast is an anti-inflammatory. Identifying the ability of ibudilast to reverse these would provide a therapeutic framework for addressing the distinct adverse consequences experienced by veterans with TBI who receive opioids for pain management in the rehabilitative period.