A recent study by Northwestern Medicine reveals that within just one to three days after a whiplash injury, researchers can determine which patients are likely to experience chronic pain. This prediction is based on the interactions between two brain areas and the individual’s anxiety levels post-injury.
The research demonstrated that the more communication there is between the hippocampus, which handles memory, and the cortex, responsible for long-term memory storage, the greater the likelihood of developing chronic pain. Furthermore, the higher a person’s anxiety immediately following a car accident, the more accurately scientists could foresee the chronic pain reported a year later.
This study is the first to highlight that changes in the brain shortly after an injury can indicate a potential risk for chronic pain development.
The findings will be published on October 24 in Nature Mental Health.
According to the study’s lead author, Paulo Branco, who is an assistant professor of anesthesiology and pain medicine at Northwestern University Feinberg School of Medicine, the dialogue between the hippocampus and cortex likely helps form new memories related to the accident and pain. “The hippocampus is essential for turning new experiences into lasting memories,” he noted.
While the reasons behind this heightened connectivity as a risk factor for chronic pain remain unclear, the researchers suggest that individuals may have formed a strong memory connecting head and neck movement to pain.
“This creates expectations and associations,” Branco explained. “If the memory is charged with emotion, the individual is more likely to associate that movement with pain. When the brain receives signals related to these memories, it pays greater attention to them due to the painful associations from the accident.”
“We often think of pain as strictly connected to an injury, but it’s actually the brain that creates the pain experience,” he stated. “The brain determines whether a movement feels painful and this decision might depend on past experiences stored in memory.”
Understanding the Timing of Chronic Pain for Better Prevention
“With this knowledge about the critical time frame for these changes, we can tailor our treatment approaches to focus on prevention during this early stage, rather than attempting to resolve chronic pain later, which is often a greater challenge,” stated Apkar V. Apkarian, the study’s corresponding author and director of the Center for Translational Pain Research at Northwestern University Feinberg School of Medicine.
“As anxiety significantly influences brain changes, addressing this anxiety soon after the injury could potentially prevent these changes using anti-anxiety medications or other treatments,” Apkarian added. “Future innovative treatments might target hippocampal activity and connectivity through drugs or neuromodulation methods.”
The Apkarian lab has previously shown that, beyond the physical aspects of the injury itself, the brain plays a crucial role in developing and sustaining chronic pain. However, understanding the mechanisms behind this has been lacking until now. How does the brain predispose patients to chronic pain? Is there a specific period when brain changes occur that heighten the risk? This study provides answers to those inquiries.
Chronic pain represents a substantial challenge for society, deeply affecting millions worldwide, both physically and emotionally. In the U.S., an estimated 3.3 million adults experience chronic pain following whiplash, along with many others who suffer from different chronic pain conditions. Current pain management options are limited and often inadequate, leading many patients to rely on opioids, which contributes to the ongoing opioid crisis.
Study Methodology
This extensive longitudinal study was carried out through a partnership between Technion-Israel Institute of Technology, Northwestern University, and McGill University. Researchers gathered the largest longitudinal brain imaging dataset to date, involving over 200 whiplash patients, with 177 completing MRI assessments. The aim was to discover early indicators of the shift from acute to chronic pain. This patient demographic offered a rare chance to study early brain changes post-injury, as pain can often be linked directly to the moment of the accident. Data collection spanned from March 2016 to December 2021.
Patients participated in functional magnetic resonance imaging within three days of their injury, enabling researchers to look at brain activity in areas associated with learning and memory at this crucial time. They were monitored over the subsequent year to evaluate pain levels and identify who developed chronic pain versus those who recovered. Participants also completed a wide range of psychological and psychophysical assessments to enhance the findings from brain imaging.
Future Directions in Research
In the short term, researchers plan to explore the mechanisms driving hippocampal responses post-injury by evaluating additional factors such as physiological (cortisol, inflammation) and psychological (trauma, stress-related disorders, fear of movement) influences that could impact these brain processes. They also seek to determine if these findings apply to other chronic pain conditions. Ultimately, the aim is to address maladaptive responses early following an injury to evaluate their causal role in chronic pain development, potentially employing pharmacological approaches, cognitive-behavioral therapy, or transcranial magnetic stimulation.
This research received funding from the Department of Defense (W81XWH-15-1-0603), the National Institute on Drug Abuse (P50DA044121), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR074274), all part of the National Institutes of Health.
