brain mapping

Scientists uncover brain “hot spots” that point to a cure for chronic pain

Brain scans bring scientists one step closer to better treatment.

The experience of consistent pain is one that's typically associated with the elderly — the stereotype being that when you're older, everything hurts.

However, chronic pain actually impacts an estimated one in seven people between the ages of 18 to 25. This is pain that can last for months — even years. In some cases, the cause is an injury or infection. In other cases of chronic pain, there's no clear cause.

Because chronic pain is “invisible” and poorly understood, sufferers say medical providers are quick to downplay its severity, making it hard to get a correct diagnosis or effective treatment.

But a new study suggests that effective treatment is likely on the horizon. Armed with the brain scans of 68 people with back pain, scientists have identified “hot spots” linked to chronic pain in the brain. These target areas could help clinicians better diagnose and treat chronic pain — improving the lives of 50 million people in the process.

The discovery could be game-changing for people like Cheyenne MacDonald, Input's news editor. MacDonald recently described her chronic pain in the article "Living with chronic pain is hell."

"Fatigue I’d attributed to overworking swallowed me whole; the aching in my chest became the stabbing, emergency room kind; and the sun felt like a mortal enemy,” MacDonald writes.

Her experience matches that of others with chronic pain, according to co-author Paul Geha, a psychiatrist at the University of Rochester Medical Center

"Chronic pain can be very debilitating because it factors into everything in life," Geha tells Inverse.

In turn, Geha views his team's discovery as a "message of hope" to the millions of patients who suffer from chronic pain.

"We are getting closer to an objective diagnosis and to the identification of critical targets for novel treatments," Geha says.

This research was published Wednesday in the journal Proceedings of the National Academy of Sciences.

Traditionally, the study of pain has revolved around the idea that if you fix the underlying injury, chronic pain goes away.

However, Geha says that this approach misses the fact that the nervous system is "not a simple passive observer or detector of injury." Instead, pain causes the nervous system to undergo significant changes — from the site of the actual injury, like a torn muscle, all the way to the brain. These signals to the brain, in turn, are thought to influence decision-making — like choosing whether or not to stay in bed because your back hurts.

To make matters more complicated for researchers, there's no brain region responsible pain. Instead, "an extremely low percentage of neurons" drive the sensation of pain when they are stimulated, Geha explains.

"We still do not know how pain arises in the brain," he says.

But in the past two decades, with the advent of brain-scanning technology, research on the neurological roots of chronic pain has exploded. Two recent studies suggest the limbic system, which deals with emotion, memory, and decision-making, plays a critical role.

In this new study, Geha and his team explored the structure and function of the limbic system in 30 healthy people, 40 people with subacute back pain (pain that's persisted between six weeks and three months), and 28 people with chronic low back pain (pain that's lasted over three months).

They specifically examined four parts of the brain: the amygdala, nucleus accumbens, thalamus, and hippocampus.

Using functional magnetic resonance imaging, the researchers measured subcortical brain volumes of these regions and brain activity. They also tracked whether healthy people or those with subacute pain went on to develop chronic pain.

The brain scans revealed that the volume of the nucleus accumbens is smaller in the brains of people with subacute back pain and chronic back pain.

When it came to individuals whose subacute back pain turned into chronic back pain, the volume of the nucleus accumbens remained small, in comparison to healthy people and those whose back pain went away. These structural differences existed before the chronic pain set in.

Left nucleus accumbens volume shows a gradual and significant decrease when comparing subacute back pain patients and chronic low back pain patients to healthy controls


The researchers found no significant differences in the hippocampus, thalamus, or amygdala volumes between healthy participants and back pain patients.

"We are closer to a diagnostic test that would be similar to a pregnancy test but for chronic pain."

The team also found differences in how the brains functioned: Back pain patients lost low-frequency fluctuations (0.01 to 0.027 Hertz) in the nucleus accumbens, as pain transitioned from subacute to chronic.

These frequency fluctuations could be "signatures" of chronic pain and effective markers for diagnosis, the researchers report.

These findings are important due to their robustness and reproducibility, Geha says.

"We are closer to a diagnostic test that would be similar to a pregnancy test but for chronic pain," he predicts.

A cure for chronic pain doesn't exist yet — but research like this makes that goal more likely to materialize. In the meantime, Geha offers advice to people with chronic pain.

"Try to keep your brain as healthy as possible by exercising, eating healthy and going to mental health therapy if need be," Geha says. Not taking these steps can decrease neural resilience, he says, which "invariably worsens the chronic pain experience."

Abstract: Chronic pain is a highly prevalent disease with poorly understood pathophysiology. In particular, the brain mechanisms mediating the transition from acute to chronic pain remain largely unknown. Here, we identify a subcortical signature of back pain. Specifically, subacute back pain patients who are at risk for developing chronic pain exhibit a smaller nucleus accumbens volume, which persists in the chronic phase, compared to healthy controls. The smaller accumbens volume was also observed in a separate cohort of chronic low-back pain patients and was associated with dynamic changes in functional connectivity. At baseline, subacute back pain patients showed altered local nucleus accumbens connectivity between putative shell and core, irrespective of the risk of transition to chronic pain. At follow-up, connectivity changes were observed between nucleus accumbens and rostral anterior cingulate cortex in the patients with persistent pain. Analysis of the power spectral density of nucleus accumbens resting-state activity in the subacute and chronic back pain patients revealed loss of power in the slow5 frequency band (0.01 to 0.027 Hz) which developed only in the chronic phase of pain. This loss of power was reproducible across two cohorts of chronic low-back pain patients obtained from different sites and accurately classified chronic low-back pain patients in two additional independent datasets. Our results provide evidence that lower nucleus accumbens volume confers risk for developing chronic pain and altered nucleus accumbens activity is a signature of the state of chronic pain
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