Early brain changes predict chronic pain after whiplash injuries

A new study has found that within just a few days of a whiplash injury, it is possible to predict which patients are likely to develop chronic pain based on brain activity and anxiety levels. Researchers discovered that the level of communication between the hippocampus, which is involved in memory, and the cortex, responsible for storing long-term memories, is a key indicator. Additionally, individuals with higher anxiety shortly after the injury were more likely to report chronic pain a year later. The findings, published in Nature Mental Health, suggest early interventions could prevent chronic pain before it becomes entrenched.

Chronic pain affects millions of people worldwide and remains one of the most challenging health conditions to treat. Whiplash injuries, often caused by car accidents, provide a unique opportunity to study pain progression because the onset of symptoms can be precisely traced to the time of the injury. The researchers aimed to better understand the brain’s role in the transition from acute to chronic pain. Specifically, they focused on the hippocampus, a brain region critical for memory formation, to examine how its interactions with other brain areas could influence pain outcomes.

Previous research has suggested that chronic pain is driven by maladaptive emotional learning, where the brain forms strong negative associations with certain experiences, such as movement or touch. This study sought to uncover the mechanisms behind this process, particularly during the critical early stages after an injury. Understanding these mechanisms could lead to treatments that interrupt the development of chronic pain, offering hope for millions of patients.

“Chronic pain remains a major source of disability worldwide, and treatment options remain inadequate. The main logic of this investigation is an effort to better understand mechanisms of chronic pain, which we hope will lead to new treatment options to both prevent the transition to chronic pain and more efficiently manage chronic pain,” said corresponding author Apkar V. Apkarian, director of the Center for Translational Pain Research and a professor of neuroscience at Northwestern University Feinberg School of Medicine.

“Our previous work shows that brain properties and mechanisms are important to understanding chronic pain, especially emotional learning circuits. However, the role of these systems immediately after an acute injury has remained unknown. The hippocampus is the brain region critical for memory formation and memory consolidation, yet its role in chronic pain has been minimally understood. Therefore, we studied its involvement in subjects who experienced a car accident with minimal injuries but severe enough to seek medical help.”

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The study was a collaborative effort between Northwestern University, McGill University, and the Technion-Israel Institute of Technology. Researchers followed 110 participants who sought medical care after car accidents resulting in minor injuries, such as whiplash. These participants, who were otherwise healthy prior to the accident, underwent functional magnetic resonance imaging within three days of the injury. This timing allowed the researchers to examine brain activity during the acute phase of pain.

“We specifically focused on subjects who had a car accident, as they were experiencing an acute traumatic event and acute pain, most likely after leading a healthy life,” Apkarian noted. “Thus, in these subjects, there is no bias due to preexisting pain conditions that may complicate explaining the results.”

Participants also completed psychological and physical tests to assess their anxiety levels, pain intensity, and other factors. Over the next year, the researchers tracked their progress, recording whether their pain resolved or became chronic. By combining brain imaging data with psychological assessments, the team identified patterns that distinguished those who recovered from those who developed long-term pain.

One of the study’s most innovative aspects was its use of brain connectivity analysis. The researchers focused on how the hippocampus interacted with the cortex and other brain regions associated with emotion and memory, such as the amygdala. These connections were evaluated for their potential role in predicting chronic pain.

The results revealed a connection between brain activity and chronic pain outcomes. Participants who developed chronic pain showed increased communication between the hippocampus and the cortex shortly after their injury. This heightened connectivity appeared to reflect the formation of strong, emotionally significant memories linking specific movements or sensations to pain. Researchers hypothesize that these memories create persistent expectations of pain, which reinforce the chronic condition.

“These results indicate that psychological and brain responses to a car accident within the first few days determine long-term chances of developing chronic pain,” Apkarian told PsyPost. “The practical implication of the study is that early proper treatments can interrupt the transition to chronic pain. Thus, we need to identify what early procedures or drug treatments can stop this process.”

Anxiety also appeared to play a significant role. Individuals with higher levels of anxiety in the first few days after the accident were more likely to report chronic pain one year later. The combination of heightened brain connectivity and anxiety provided a powerful predictor of chronic pain development.

The findings challenge traditional views of pain as merely a physical response to injury. Instead, they highlight the brain’s role in shaping the pain experience, suggesting that psychological and neurological factors are just as important as physical damage.

“These results imply that emotional learning and emotional memory acquisition and storage are critical to the development of chronic pain,” Apkarian said. “These findings suggest that appropriate treatments can be devised and tested. Also, we can design future studies to begin to understand how these early events affect other brain processes that create chronic pain.”

While the study provides valuable insights, it has some limitations. First, the researchers focused on whiplash injuries, which may limit the generalizability of their findings to other types of chronic pain. Additionally, the study did not account for medication use after the accident, which could have influenced pain outcomes. Finally, while the hippocampus was a primary focus, other brain regions likely contribute to chronic pain and warrant further investigation.

Future research will explore the underlying mechanisms behind these brain changes. For example, researchers plan to study how factors like inflammation, stress hormones, and psychological trauma interact with the hippocampus to influence pain outcomes. They also aim to test whether these findings apply to other chronic pain conditions, such as fibromyalgia or back pain.

“Our long-term goals are to continue to understand brain mechanisms that determine the development of chronic pain,” Apkarian said. “Based on such results, we also hope to identify drug targets for either blocking the development of chronic pain or treating chronic pain.”

The study, “Hippocampal functional connectivity after whiplash injury is linked to the development of chronic pain,” was authored by Paulo Branco, Noam Bosak, Andrew D. Vigotsky, Yelena Granovsky, David Yarnitsky, and A. Vania Apkarian.