Researchers have for the first time recorded the brain’s activation patterns while a person feels chronic pain, paving the way for implanted devices to one day predict or even short-circuit pain signals.
Using a pacemaker-like device surgically placed in the brain, scientists recorded four patients who had had persistent nerve pain for more than a year. The devices recorded several times a day for up to six months, providing clues to where chronic pain is located in the brain.
The study, published Monday in the journal Nature Neuroscience, reported that the pain was linked to electrical fluctuations in the orbitofrontal cortex, an area involved in emotion regulation, self-evaluation and decision-making. The research suggests that such patterns of brain activity could serve as biomarkers to guide diagnosis and treatment for millions of people with shooting or burning chronic pain related to a damaged nervous system.
“The study really advances a whole generation of research that has shown that brain functioning is really important for processing and perceiving pain,” said Dr. Ajay Wasan, a pain medicine specialist at the University of Pittsburgh School of Medicine, who was not involved in the study.
About one in five American adults experiences chronic pain, that is, persistent or recurrent pain that lasts more than three months. To measure pain, doctors usually rely on patients to rate their pain, using either a numerical scale or a visual scale based on emojis. But self-reported pain measures are subjective and can vary throughout the day. And some patients, such as children or people with disabilities, may have trouble communicating accurately or rating their pain.
“There’s a big movement in the pain field to develop more objective markers of pain that can be used in addition to self-reporting,” said Kenneth Weber, a neuroscientist at Stanford University, who was not involved in the study. In addition to increasing our understanding of what neural mechanisms underlie pain, Dr. Weber added, such markers could help validate the pain some patients experience that is not fully appreciated — or even outright ignored — by their doctors.
Previous studies had mostly scanned the brains of chronic pain patients to observe changes in blood flow in different regions, an indirect measure of brain activity. However, such research is limited to laboratory settings and requires patients to visit a hospital or laboratory multiple times.
In the new study, Dr. Prasad Shirvalkar, a neurologist at the University of California, San Francisco, and his colleagues instead used electrodes to measure the collective firing pattern of thousands of neurons near the electrodes.
The researchers surgically implanted the recording devices in four people who had been living with pain for more than a year and had not found relief from medication. In three of the patients, the pain started after a stroke. The fourth had so-called phantom pain after losing a leg.
At least three times a day, patients rated the pain they felt and then pressed a button that prompted their implants to record brain signals for 30 seconds. By monitoring patients daily, at home and at work, “this is the first time ever to measure chronic pain in the real world,” said Dr. Shirvalkar.
The researchers placed electrodes in two brain regions: the orbitofrontal cortex, which hasn’t been much studied in pain research, and the anterior cingulate cortex, a region involved in processing emotional signals. Many studies have suggested that the anterior cingulate cortex is important for the perception of both acute and chronic pain.
The scientists fed the data on the patients’ pain scores and associated electrical signals into machine learning models, which were then able to predict high and low chronic pain states based on brain signals alone.
The researchers found that certain frequency fluctuations of the orbitofrontal cortex were the best predictors of chronic pain. While that brain signature was common among patients, Dr. Shirvalkar, each patient also showed unique brain activity. “Each patient actually had a different fingerprint for their pain,” he said.
Given these variations and only four study participants, Tor Wager, a neuroscientist at Dartmouth College who was not involved in the study, suggested caution in duplicating orbitofrontal cortex signatures as biomarkers.
“We certainly want to confirm this with other studies using other methodologies that can provide systematic coverage of the whole brain,” he said.
The study authors also noted that other brain regions may be involved. “We’re just getting started,” says Dr. Edward Chang, a neurosurgeon at the University of California, San Francisco. “This is only chapter one.”
The implants have another purpose: deep brain stimulation. As part of a larger clinical trial to treat chronic pain, Dr. Shirvalkar and his colleagues use mild electrical currents to stimulate brain regions near the electrodes. In addition to the four patients in the study receiving this experimental therapy, the researchers aim to recruit two more people and eventually expand the study to 20 or 30 people. The researchers hope to relieve patients’ persistent pain by sending pulses through the electrodes to correct any abnormal brain activity.
