For the first time scientists have followed a group of people with the same new back injury over time and found brain scans of those who go on to have chronic back pain, appear to show a different pattern in the region that handles emotional responses. They suggest their discovery, which relies on fMRI scans to detect early brain changes, may serve to predict which patients are at higher risk for chronic pain, and help develop drugs to prevent it.

Writing about their work in a Brief Communication in Nature Neuroscience, A Vania Apakarian, professor of physiology at Northwestern University Feinberg School of Medicine in Chicago in the US, and colleagues, show for the first time that the more cross-talk there is between two particular brain regions, the greater the chance of the pain becoming chronic.

The two parts of the brain they refer to are the insula, which is active when people have emotional responses to events, and the nucleus accumbens, which plays a role in teaching the brain how to respond to changes in the environment.

Apakarian, whose lab has been researching chronic back pain in relation to changes in brain activity for quite a while, told the press:

“For the first time we can explain why people who may have the exact same initial pain either go on to recover or develop chronic pain.”

The injury by itself is not enough to explain the ongoing pain. It has to do with the injury combined with the state of the brain. This finding is the culmination of 10 years of our research,” he added.

In previous studies, researchers have compared the brains of people with chronic back pain to those of healthy people, but due to limitations of study design it has not been possible to pinpoint the factors that drive the pain’s chronic nature.

For example, one limitation is comparing snapshots at one point in time makes it difficult to distinguish the causes of chronic pain from the consequences, such as changes in lifestyle, and medication. The most you can find with such cross-sectional designs is links, and just suggest potential drivers. You need to conduct longitudinal studies that take several measures over time, to be more confident of what the causes might be.

For their longitudinal study, Apkarian and colleagues recruited 39 people with clinically diagnosed subacute or moderate back pain that was persistent and had begun 1 to 4 months earlier. None had a previous history of back pain.

The participants underwent assessment at the start of the study and at three more visits over the following year. During these assessments the researchers took fMRI scans of their brains and asked them to rate the level of their pain.

By the end of the 12 months, 20 of the participants had recovered, and 19 continued to experience pain, thus meeting the definition of chronic pain.

Apkarian and colleagues said there was a much higher level of cross-talk between the insula and the nucleus accumbens brain regions in the participants whose back pain persisted compared to those whose pain subsided.

And they could see that this increased communication between the two brain regions was present right at the start of the study, suggesting those scans could be used to predict which patients would be the ones whose backpain was going to persist.

When they did the analysis, they found these early scans had an 85% accuracy in predicting which participants would still be in pain by the end of the 12 months.

They suggest that the more emotionally the brain reacts to the initial injury, the greater the chance of the pain becoming chronic.

While they did not look into the reasons for this, Apkarian speculates that it could be these “sections of the brain are more excited to begin with in certain individuals, or there may be genetic and environmental influences that predispose these brain regions to interact at an excitable level”.

The nucleus accumbens helps teach the rest of the brain how to evaluate and react to the outside world, said Apkarian, so it could be that it uses the pain signal to teach the rest of the brain to develop chronic pain.

He and his colleagues also observed that the brains of the participants who went on to develop chronic pain lost gray matter density, which indicates loss of parts of the brain that are important for communication between brain cells, such as synapses that link brain cells, brain cells themselves and glial cells, that support brain cells.

“Now we hope to develop new therapies for treatment based on this finding,” Apkarian added.

More than half of Americans live with chronic or recurrent pain, the most common being headache, back pain, and neck pain, says the American Academy of Pain Medicine.

Pain is a major driver of visits to physicians, the main reason people take medication, a major cause of disability, and a key factor in quality of life and productivity, says a report published by the National Academies Press last year, that also estimates chronic pain in the United States costs up to $635 billion a year in medical treatment and lost productivity.

The report calls for relieving pain to be made a “national priority”, in order to remove the burden it places on “human lives, dollars, and social consequences”.

Written by Catharine Paddock