Chronic pain can be predicted as early as three days after an injury.

Within just one to three days of a whiplash injury, scientists can predict which patients are likely to develop chronic pain based on the level of communication between two brain regions and the patient’s anxiety levels, according to a new study by Northwestern Medicine.

The study found that the more the hippocampus, the brain’s memory center, communicated with the cortex, which is involved in long-term memory storage, the higher the likelihood of chronic pain development. Additionally, higher levels of anxiety immediately following the injury allowed for a more accurate prediction of chronic pain one year after the accident.

This groundbreaking research is the first to demonstrate that brain adaptation only days after an injury can increase the risk of developing chronic pain. The study’s findings will be published in Nature Mental Health on October 24, 2024.

According to Paulo Branco, assistant professor of anesthesiology and pain medicine at Northwestern University Feinberg School of Medicine and the study’s first author, the communication between the hippocampus and cortex likely reflects the formation of new memories related to the accident and pain. “The hippocampus is responsible for consolidating new memories into long-lasting ones,” Branco explained.

While the researchers do not fully understand why this heightened connectivity is a risk factor for chronic pain, they hypothesize that the brain may encode a strong memory linking head and neck movement with pain. This association could lead patients to anticipate pain during such movements, reinforcing the painful memory and increasing attention to these signals.

“Pain is not only about the injury itself but also how the brain interprets it,” Branco said. “The brain decides whether a movement should be painful, and this decision may rely on past experiences stored in memory.”

Implications for Treatment and Prevention

“Now that we know this critical time period exists, we can focus on early interventions to prevent chronic pain, which is far easier than trying to cure it later,” said Apkar V. Apkarian, the study’s corresponding author, director of the Center for Translational Pain Research, and professor of neuroscience at Northwestern University Feinberg School of Medicine.

Since anxiety plays a key role in these brain changes, Apkarian suggests that targeting anxiety right after the injury—through anti-anxiety drugs or other treatments—may prevent the development of chronic pain. Future treatments could also target hippocampal activity and brain connectivity through medications or neuromodulation techniques.

Previous research from Apkarian’s lab has shown that the brain, beyond injury factors, plays a crucial role in the development and persistence of chronic pain. This study helps answer longstanding questions about how the brain predisposes certain individuals to chronic pain and identifies a critical period when these changes occur.

The Study

The large-scale longitudinal study, conducted in collaboration with the Technion-Israel Institute of Technology, Northwestern University, and McGill University, involved over 200 whiplash patients, 177 of whom completed MRI testing. The study, which ran from March 2016 to December 2021, sought to identify early predictors of the transition from acute to chronic pain. The research team collected functional magnetic resonance imaging (fMRI) data within three days of injury to observe brain activity in regions associated with learning and memory. Patients were then monitored for 12 months to assess pain levels and determine which individuals developed chronic pain.

In addition to brain imaging, participants underwent a wide range of psychological and physical tests to complement the imaging data.

Next Steps

Moving forward, the researchers aim to further investigate the mechanisms behind the hippocampal response to injury by exploring additional physiological (e.g., cortisol, inflammation) and psychological (e.g., trauma, fear of movement) factors. They will also examine whether these findings can be generalized to other chronic pain conditions. In the long term, the goal is to intervene early after injury to prevent chronic pain by targeting these maladaptive brain responses through pharmacological treatments, cognitive-behavioral therapy, or transcranial magnetic stimulation.