Researchers have for the first time recorded the brain’s trigger patterns when a person experiences chronic pain, paving the way for implanted devices to one day predict pain signals or even bypass them.
Using a pacemaker-like device surgically placed inside the brain, scientists recorded four patients who had experienced incessant nerve pain for more than a year. The devices recorded multiple times a day for up to six months, offering clues to the location of chronic pain in the brain.
The study, published Monday in the journal Nature Neuroscience, reported that pain was associated with electrical fluctuations in the orbitofrontal cortex, an area involved in emotion regulation, self-evaluation and decision-making. Research suggests that such patterns of brain activity could serve as biomarkers to guide the diagnosis and treatment of millions of people with chronic throbbing or burning pain related to a damaged nervous system.
“The study really advances a whole generation of research that has shown that brain function is really important in processing and perceiving pain,” said Dr Ajay Wasan, a pain medicine specialist at the University of Pittsburgh School of Medicine, which wasn’t involved in the study.
In regards to One out of five American adults suffer from chronic pain, which is persistent or recurring pain that lasts more than three months. To measure pain, doctors typically rely on patients to rate their pain, using either a numerical scale or a visual scale based on emojis. But self-reported pain measurements are subjective and can vary throughout the day. And some patients, like children or people with disabilities, may have trouble communicating or accurately assessing their pain.
“There’s a big push in the pain field to develop more objective markers of pain that can be used alongside self-reports,” said Kenneth Weber, a neuroscientist at Stanford University, who didn’t. participated in the study. In addition to advancing our understanding of the neural mechanisms that underlie pain, Dr. Weber added, such markers can help validate pain experienced by some patients that is not fully appreciated – or even outright ignored – by their doctors.
Previous studies have typically scanned the brains of chronic pain patients to observe changes in blood flow to various regions, an indirect measure of brain activity. However, such research is limited to laboratories and requires patients to visit a hospital or a laboratory several 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 into four people who had been living with pain for more than a year and had found no relief from medication. For three of the patients, the pain started after a stroke. The fourth suffered from so-called phantom limb pain after losing a leg.
At least three times a day, patients rated the pain they felt, then pressed a button that prompted their implants to register brain signals for 30 seconds. By following patients daily, at home and at work, “this is the first time that chronic pain has been measured in the real world,” Dr. Shirvalkar said.
The researchers placed electrodes in two areas of the brain: the orbitofrontal cortex, which hasn’t been studied much in pain research, and the anterior cingulate cortex, a region involved in processing emotional signals. Many studies suggested that the anterior cingulate cortex is important for perceiving acute and chronic pain.
The scientists fed data on patients’ pain scores and corresponding electrical signals into machine learning models, which could then predict high and low chronic pain states based on brain signals alone.
The researchers found that certain frequency fluctuations in the orbitofrontal cortex were the best predictors of chronic pain. While this brain signature is common among patients, Dr. Shirvalkar said, 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 participants in the study, Tor Wager, a neuroscientist at Dartmouth College who was not involved in the study, suggested caution in doubling the signatures of the orbitofrontal cortex as biomarkers.
“We definitely want to corroborate 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 regions of the brain may be involved. “We’re just getting started,” said Dr. Edward Chang, a neurosurgeon at the University of California, San Francisco. “This is only the first chapter.”
Implants have another purpose: deep brain stimulation. As part of a larger clinical trial to treat chronic pain, Dr. Shirvalkar and his colleagues are using mild electrical currents to stimulate regions of the brain near electrodes. In addition to the four study patients who are receiving this experimental therapy, the researchers aim to recruit two additional people and possibly expand the study to 20 or 30 people. Researchers hope to relieve patients’ lingering pain by sending pulses through the electrodes to correct any aberrant brain activity.