By Jen Christensen, CNN
(CNN) — Edward Mowery lived with excruciating pain for years: Picture being put into a hot frying pan, he said, and then someone holding you down on that pan forever. The fiery, shooting pain got so bad that he quit his job, stopped playing sports and had to abandon his beloved death metal band just as the group was taking off.
“At one point, I didn’t have any feeling in my arms or hands or anything,” said Mowery, 55, who lives in New Mexico. “I couldn’t put one note on a guitar, much less play like I do.”
But everything changed when doctors tried a cutting-edge approach to pain management. If they can refine the technique to make it less intrusive and demonstrate that it works on others, doctors think this technique could radically transform the way people manage debilitating and otherwise untreatable chronic pain — no opioids or pain blockers required.
“The state of the art right now for picking a medication for an individual patient is trial and error” when it comes to pain, said Dr. Prasad Shirvalkar, a neurologist at the University of California San Francisco. “Trying to be your own guinea pig, that’s essentially what we’re doing right now in pain medicine.” Finding something more precise that could stop a pain signal in the brain before it could be felt in the body would be a huge shift.
An estimated 50 million adults in the United States experience chronic pain, defined as lasting for more than three months. Of them, about 8.5% are like Mowery, living with chronic pain that interferes with day-to-day life, according to the US Centers for Disease Control and Prevention.
Years of agony
Mowery says he was a rambunctious kid and got injured a lot while skiing and playing soccer.
Altogether he says he’s had 34 surgeries, including 11 painful knee surgeries, as well as foot, back and neck surgeries. The bigger problem, though, started with a part of his body that hadn’t even been injured.
About a week after a routine knee replacement in 2009, his right foot started to feel like it was on fire.
He spoke with “all kind of doctors, trying to figure out what was going on,” but nobody could explain the pain. Some didn’t even believe that he was in pain, assuming he was an opioid addict looking for pills. “That’s the one thing, when they put me on all these meds, I wasn’t addicted to all the meds, I was addicted to getting rid of the pain,” he said.
For eight long years, he said, doctors couldn’t figure out what was causing the pain. But in 2017, when his foot turned purple and black, he went to a pain specialist in Albuquerque who took one look and told him he had complex regional pain syndrome, or CRPS.
CRPS is a kind of neurological pain, often in the extremities, that can develop after a surgery, stroke, injury or heart attack that is out of proportion to the severity of an initial injury. It can make blood vessels dilate or constrict, leading to skin discoloration, swelling and temperature changes.
Mowery says doctors explained that when the acute pain from his knee went away, his brain essentially missed that feeling.
“Because I’d been in pain for so long, my brain was so used to being in pain that it said, ‘Oh, you need to have this back,’ ” he said. “Manufactured pain from the brain with no stimulus. It’s unreal.”
Doctors put him on a variety of pain medications, including morphine and oxycodone, that he didn’t like because he felt so out of it. At one point, he took 17 pills a day, but nothing worked for long. Always athletic, Mowery ended up relying on a walker or a wheelchair to get around.
“It’s really depressing. You would think they’d call CRPS the suicide disease,” Mowery said. “A lot of times, I was sitting there just going, ‘what am I going to do? There’s nothing out there for me.’ “
He spent years searching the internet for clinical trials and finally found one at the University of California San Francisco. The description of the research seemed vague but he filled out the questionnaire anyway and, within 40 minutes, he said, he got a message urgently asking him to come to San Francisco.
Relief from his years of agony would soon come after doctors persuaded him to let them drill several holes in his head.
‘These are people that have been failed’
Shirvalkar says he has long wanted to solve the puzzle that is pain. He had success treating neurological conditions but less success treating their chronic pain.
“There are people that have been failed by all available therapies. They’ve tried over 25 different medications. They have had multiple injections and nerve blocks.
They’ve even had spinal cord stimulators or peripheral stimulators, and nothing can alleviate their suffering,” Shirvalkar said. “We started appreciating that the brain must be generating or perpetuating these pain signals in a person. So the question becomes, how can we identify what these signals are and really try to suppress or short-circuit them?”
Acute pain, like when someone stubs a toe, affects the brain differently from chronic pain, he said.
“I think of chronic pain as a fire alarm. The alarm is helpful for acute pain. We want to be able to know when there’s an emergency,” he said. “In chronic pain, it’s as if the fire alarm is going off, but we can’t identify the fire.”
When pain becomes chronic, it rewires the brain.
“It starts to take on these other dimensions that include mood and motivation and involve attention and memory, and so we really have to address the cognitive aspect of it,” Shirvalkar said. “It tells me that when someone has developed chronic pain, treating it with a single drug or injection or some monotherapy probably isn’t going to work.”
With the help of a $7.56 million grant from the National Institutes of Health, Shirvalkar and a team at UCSF have been exploring deep brain stimulation, a technology sometimes used with people who have Parkinson’s disease, to treat pain conditions like Mowery’s.
With Parkinson’s, doctors implant electrodes in the brain that produce electrical impulses to disrupt the abnormal signals that cause tremors, stiffness and slow movement. Shirvalkar wondered if they could also use the a version of the device to redirect or suppress the brain’s pain signals to the body.
There were a few challenges with this approach. The device sends signals around the clock in someone who has Parkinson’s, but Shirvalkar thought a constant signal wouldn’t work for chronic pain because the brain can become acclimated to the impulses and essentially override them.
Another challenge was figuring out what part of the brain was sending pain signals.
There’s no one central location that does this, and it could be different in different people.
Yet another challenge would be to quickly sense when the brain was about to send out a pain signal – or even anticipate it – and shut it down quickly.
The team used computational models and AI to essentially detect a biomarker that could track how severe a person’s chronic pain would be, similar to how an A1C level can tell whether someone has diabetes and how severe it is.
But to learn whether deep brain stimulation could work for pain, the team first had to persuade Mowery that he should have another surgery. He was reluctant to have another procedure. This trial would require three.
‘I feel like I owe him my life’
It took Mowery about 18 months to decide the trial was right for him – time in which the worsening pain essentially wore him down.
In the first surgery, doctors would map Mowery’s brain to determine where the pain came from. Another surgery would remove the temporary probes from the first procedure. A final procedure placed permanent probes in the correct areas.
For the first part of the trial, Mowery spent 10 days in the hospital while doctors created a grid of more than 100 points on his head to try to find different circuits or certain activation for pain by watching and stimulating his brain. Even with eight- to 10-hour days probing his brain, it wasn’t until day five or six that the researchers had their “eureka moment.”
“All of a sudden, Ed says, ‘Wow, my pain just washed off of me,’ ” Shirvalkar said. “I was blown away. I didn’t know what to say.”
Concerned that it could be the placebo effect, the doctors kept testing to make sure they had the right targets. Shirvalkar quickly became confident that they had picked the right areas when Mowery immediately felt the pain in his feet, legs and lower back dissipate.
“When it comes to actually understanding what’s driving someone’s chronic pain, we say there’s no pain center, right? But it tells us if chronic pain is this complex lock, it tells us that yes, that there is a key to be found. So it gives us hope.”
Much more research will be done to see if this technology can work for everyone or whether there would be even better technology that would be less invasive.
In August, Shirvalkar and his team published the results of their tests of this technique on six people. The team followed the patients for 22 months and were even able to randomize the trial so some got the stimulation and some did not. Those who got stimulation reported a reduction in pain of about 60%, while the placebo group got no such relief.
Mowery has resumed his normal daily activities, including playing his guitar. He can monitor what’s going on in his brain with an iPad app and just has to periodically charge the device that sends the signals to his brain.
He’s not totally pain-free, he says: He’ll have a bad day sometimes, but it’s infrequent.
He says Shirvalkar’s work changed his life.
“The way it detected pain, the way it turns off pain, the way I’m getting off all these medications, I feel like I owe him my life,” Mowery said.
Mowery felt so much better that, in June, he accompanied Shirvalkar to Washington to testify before Congress’ Neuroscience Caucus about the impact of the NIH BRAIN Initiative on addiction research and on this pain treatment alternative.
Shirvalkar is concerned about future funding amid the current political environment and other funding cuts at the NIH.
“NIH funding is always a concern. Fortunately, we’re doing OK for the time being,” Shirvalkar said. “We’ll have to wait and see.”
Mowery hopes that his experience will provide enough of an example so people can see the possibilities of such medical research.
“I have been called a medical astronaut before, and my sister is an actual astronaut, and she finds that funny,” Mowery said. “It’s a miracle.”
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