Nicole Emmitt, a post-doctoral fellow and fourth-year veterinary student in the College of Veterinary Medicine’s DVM/PhD program, recently earned top honors at the 27th Society on NeuroImmune Pharmacology (SNIP) Conference in New Delhi, India.  

A travel scholarship awardee, she attended the Early Career Investigator Travel Award Symposium where she presented her research on inflammatory immune responses in the brain following traumatic brain injury (TBI) and changes in sensitivity to, and consumption of, opiates following mild TBI. At the SNIP conference, Emmitt won the award for Outstanding Oral Presenter. 

Given the current opiate pandemic, Emmitt’s research is critical to understanding the relationship between TBI and disordered opiate use. Emmitt says she pursued this research area after she realized she could help both people and animals through her studies.

“I felt driven to utilize my understanding of research methodologies and training in veterinary medicine to help develop better and safer treatments to be used in clinical settings,” she says. 

Mild TBI affects approximately 65–75 million people each year. A history of mild brain injury has been shown to increase the risk of substance use disorder by two to six times that of the general population. Previous studies have shown that adolescents and soldiers with a history of mild TBI have a 2.5 times greater risk for substance use disorder. Less is known about opiate use following TBI in the general population because mild TBI is often underreported.

Investigating change

Emmitt’s research examined the relationship between mild TBI and opiate use. Using a mouse model, she measured levels of immune cells indicative of inflammation in the brain of mice with and without TBI—checking levels before, during, and after administration of different doses of morphine, an opiate, at days 1,3,7, and 15 following the brain injury. 

Mice who had a mild TBI were found to have higher levels of pro-inflammatory macrophages and CD8 lymphocytes, types of immune cells associated with inflammation, following the administration of morphine. Inflammatory indicators in mice with TBI were markedly changed by the administration of opiates. The function of the inflammatory cells was also altered with the administration of opiates. Changes also indicated a leakiness of the blood-brain barrier in mice with TBI following opiate use. 

In addition to measuring changes in pro- and anti-inflammatory cells in the brain, Emmitt also noted behavioral changes following the administration of morphine to mice with and without mild TBI.

Opiate-seeking behavior was observed by placing the mice in multi-compartment containers that allowed them to self-administer morphine. The mice were placed in the center compartment of the container and that compartment was flanked on either side by an accessible compartment—one paired with prior morphine exposure and the other with saline injection. 

By measuring the time a mouse spent in the compartment of the container that was paired with opiate exposure as opposed to time spent in the compartment with exposure to saline, and the amount of opiate a mouse self-administered, the research compared opiate-seeking differences in mice with and without a TBI. Mice with a TBI and opiate exposure spent more time in the area of the box providing access to morphine and also self-administered morphine at higher levels.

Findings and next steps

Emmitt’s research in a mouse model showed that inflammation in the brain following mild TBI is linked to higher levels of consumption of opiates which also correlates with an inflammatory response in the brain. Additional studies are scheduled to better understand the immune mechanisms that link opiate abuse and TBI. 

Understanding the mechanisms that lead to increased opiate sensitivity in people with TBI may help to prevent substance use disorders and deaths. More research needs to be done to understand the functional components of mild TBI and opiate use to develop treatments effective in reducing neuroinflammation and drug-seeking behavior. 

“Every study we do advances our understanding of physiology and disease that can help veterinary and human medicine,” Emmitt says. 

A comparative medicine scientist who advances science by building on differences and similarities in human and animal medicine, Emmitt plans to work as a research veterinarian upon completing her DVM, working to improve the quality of translational studies that utilize animal models. She enjoys advancing research, but she is particularly excited to continue to mentor other students who are interested in a research path. 

The National Institutes of Health National Institute on Drug Abuse reports a steady and dramatic increase in opiate-involved overdose deaths notes dating back to 2019. Opioid-involved overdose deaths rose from approximately 21,000 in 2010 to 48,000 in 2017  In 2020, death increased significantly to approximately 69,000 and jumped again in 2021 to a total of 80,411 reported overdose deaths. The importance of Emmitt’s work and the work of others seeking to better understand substance use disorders and how factors such as a history of mild TBI will be a key to fighting the opiate pandemic.  

“I am excited to learn more about advancing new treatments and technology to help animals and humans alike,” Emmitt says.  

Emmitt’s research was funded in part by the Minnesota Spinal Cord and Traumatic Brain Injury Research Grant Program, the Minnesota Office of Higher Education, the state of Minnesota, the National Research Service Award, the National Institute on Drug Abuse, the National Institutes of Health, and 2019 CVM Resident & Graduate Student Research Grants. Emmitt’s dissertation advisor was Maxim Cheeran and her co-advisor was Walter Low.