Chronic Headache Due to Mild Traumatic Brain Injury in Adults: Alterations of Brain Function, Central Sensitization, and Inflammatory Processes
Abstract
This application addresses the Fiscal Year 2017 Peer Reviewed Medical Research Program Topic Area of post-traumatic headache (PTH), with the specific area of encouragement “the pathobiology of these headaches, and the risk factors that might predispose people to post-traumatic headaches.” Mild traumatic brain injury (mTBI) is a significant health concern, affecting countless deployed and non-deployed Service members, and civilians. More than 1 million TBIs occur in civilian adults each year in the United States, with mTBIs accounting for approximately 80% of those injuries. In the military, TBI is considered a signature injury of modern warfare. Additionally, TBIs occur in military Service members during training accidents, falls, and motor vehicle accidents. Among military Service members, the majority of TBIs fall into the mild category. In the general population and military, headaches (PTHs) are one of the worst, most prominent, and longest-lasting consequences of mTBI, and seriously complicate rehabilitative efforts. Furthermore, PTH is an important cause of medical evacuation from duty and failure to return to duty in military Service members. Unfortunately, the reasons why PTHs become chronic in a substantial portion of individuals experiencing a mTBI remain poorly understood. Consequently, no specific noninvasive diagnostic techniques exist for early detection of PTH risk to facilitate the prevention and treatment of chronic PTHs. Thus, the purpose of the proposed study is to identify risk factors that predict which patients following mTBI will experience chronic PTHs (i.e., lasting more than 3 months), with a focus on dysfunctional pain processing in the central nervous system, brain abnormalities following mTBI, and inflammation. Based on prior research and our pilot data, we propose that mTBIs prime the immune system to excessively produce inflammation for extended periods of time after the injury. Elevated levels of inflammation coupled with alterations in brain structure and function following injury likely cause dysfunctional regulation of pain in the central nervous system. These deleterious effects following mTBI place these patients at high risk for the development of chronic headaches. Furthermore, we expect that patients with repeated mTBIs will show an exacerbation of risk factors for PTHs compared to patients who have experience only a single mTBI. To address the purpose of this study, we will assess severity and frequency of headaches, propensity for chronic inflammation associated with innate immune cells, the structure and function of the brain via brain imaging, and pain processing in the central nervous system via quantitative sensory tests in single and repeated mTBI patients at 1 week, 1 month, and 6 months post-injury. We will also take the same measures in individuals of similar age and sex who have not experienced a mTBI. Obtaining the knowledge described above will have a significant impact on identifying promising preventative and therapeutic strategies for persistent PTH in civilian and military populations. For example, our non-invasive assessments of the immune system and of pain regulation in the central nervous system may serve as vulnerability biomarkers for development of chronic PTH that could be determined near the time of injury and could help identify those at greatest risk for developing chronic headaches. Once potential treatment targets are identified, a second step for future research will be to test the effectiveness of mechanistic-based treatments to prevent or manage chronic PTHs. Ultimately, understanding the factors underlying the development of chronic PTH will enable the accurate prediction of which individuals will develop this debilitating consequence of mTBI long term and serve as a step forward in individualizing pain medicine for prevention and treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810434
Entities
People
- Kelly Naugle
Organizations
- Indiana University – Purdue University Indianapolis
- United States Army