Decoding the brain’s secrets: Revolutionizing chronic pain treatment

Embedded electrodes capture brain activity related to chronic pain.

Electrodes embedded in the brains of four people have captured a detailed and precise portrait of chronic pain.

The new work, published Monday in the journal Nature Neuroscience, points to brain regions that could be targeted for future treatments, neuroscientists say while adding to our understanding of why some people develop persistent, unyielding chronic pain.

Scientists surgically implanted electrodes in the brains of four study participants who had struggled with mysterious searing pain in parts of their bodies for years.

The researchers collected data for months and used machine-learning models to sift through it, ultimately pinpointing electric signals in the brain corresponding to moments of high and low chronic pain in their study participants.

The findings are a rare view of brain activity linked to chronic pain, a puzzling condition that afflicts millions of Americans. The team found that a section of the brain just behind the forehead lit up with a low hum of electrical activity when the study participants felt chronic pain.

But when participants touched a hot probe, another brain region was active, indicating that fleeting pain from an injury operates differently from chronic pain.

“Chronic pain is actually its own separate disease that is not simply an extension of pain in general,” said study author Dr Prasad Shirvalkar, a pain physician and neurologist at the University of California San Francisco Medical Center.

The study is a step toward an objective, universal measure of pain in a patient, Shirvalkar said, to augment the current method available to doctors: asking patients to rank their discomfort on a scale.

A fifth of US adults experience chronic pain, according to the Centers for Disease Control and Prevention, defined as pain felt most days or more for the past three months [1].

These could be migraines or back pain, pains linked to cancer or arthritis, or a lingering ache from an injury that has long healed. For about 19 million people, intense chronic pain restricts the ability to work or disrupts daily life.

Between 2019 and 2020, there were more new cases of chronic pain than other chronic conditions, including hypertension or diabetes, a study published this month in JAMA Network Open found [2].

People 50 or older had a higher risk of chronic pain than younger people. Most people with chronic pain didn’t recover from it until a year later.

Photograph: tommyandone/Envato

There are no effective chronic pain cures, partly because its biology is poorly understood. “Most treatments don’t work for most people most of the time,” said Tor Wager, a neuroscientist and psychologist at Dartmouth College who wasn’t involved with the work.

Arthritis or inflammation is responsible for the dull aching of some chronic pain. Misfiring neurons in the brain or nervous system are thought to drive the stabbing and burning of another type of chronic pain, including the phantom limb pain and post-stroke pain that the study participants experienced.

Wager said the orbitofrontal cortex, in which the study captured signals during periods of intense chronic pain, is among the regions most altered by cognitive behavioral therapy.

The new data makes the case for further developing psychological and behavioral approaches for chronic pain.

Deep-brain stimulation, in which electrodes deliver electric current to precise targets in the brain, has shown some promise as a treatment for Parkinson’s and depression.

The method is also being explored as a chronic-pain therapy, and the study suggests brain regions at which a current could be aimed, said Flavio Frohlich, a neuroscientist who studies brain stimulation at the University of North Carolina School of Medicine and isn’t involved with the study.

“Out of that beautiful symphony of rhythmic electrical activity patterns, we need to be honing in on that one player in the orchestra that has not tuned their instrument,” said Frohlich.

“This paper really provides some fundamental insights of where in the orchestra to look and what specific notes aren’t played properly.”

Three of the participants, in their 50s at the time of the study, had begun feeling burning pains on one side of their body after experiencing a stroke.

The fourth participant, in her 60s, had an amputation of her right leg above the knee but was feeling burning and squeezing phantom pains in her missing calf and foot. 

At least three times a day daily for three to six months, the participants were texted a pain questionnaire in which they reported their pain level at that time.

Then they turned on the implanted device, which measured electrical pulses in the brain for about 30 seconds.

The research team used machine-learning tools to find moments of high and low chronic pain in the data, matching self-reported pain levels from the participants. “The fact that it worked at all was kind of amazing,” Shirvalkar said.

In all four participants, low-frequency signals in the orbitofrontal cortex were active when experiencing high pain levels.

But the specific fingerprint—the exact combination of electric frequencies overall—was different between the participants, Shirvalkar said.  

“This is an exciting proof of concept study,” said Salimah Meghani, a pain disparities researcher at the University of Pennsylvania School of Nursing who wasn’t involved with the study. Future studies should include diverse participants, she said. 

“We know that socioeconomic risk factors and past experiences such as racial stress can have a profound impact on the experience of pain.” [3]


Photograph: primagefactory/Envato
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