Millions of Americans live with pain. While pain can be an important indicator of health, it can also be debilitating, causing fatigue, depression and a decreased quality of life. Researchers from Johns Hopkins University and George Washington University estimated that pain cost the United States $560 billion to $635 billion in 2011.
In the 1990s, pharmaceutical companies claimed they had the answer: opioids. After being assured these drugs were not addictive, doctors prescribed opioids liberally, hoping to relieve their patients’ suffering.
But opioids are highly addictive, and as doctors prescribed more and more, drug abuse escalated. Some patients turned to heroin and synthetic opioids when they couldn’t get ahold of prescription drugs, and between 1999 and 2019, opioid overdoses killed nearly 500,000 people in the U.S. In 2017, the United States Department of Health and Human Services declared the opioid epidemic a public health emergency.
Since discovering the addictive properties of opioids, scientists have been searching for safer alternatives to relieve pain. Biomedical engineer John A. Rogers, of Northwestern University, thinks he may have created one—an implantable, dissolvable device that cools nerves in the body.
“Managing pain is an important aspect of patient care in many contexts, and that is currently accomplished with various sorts of pain-killing drugs, opioids being maybe most prominent,” he says. “Those schemes work extremely well at eliminating pain, but they have various kinds of side effects—a tendency for addiction being prominent among those.”
Instead, Rogers and his team thought they could engineer a device allowing more targeted pain relief that could be ramped up or tapered down depending on pain intensity. Using cooling, the implant would numb specific peripheral nerves that connect the brain and spinal cord to the rest of the body. This measure would block pain signals to the brain, effectively regulating pain in specific parts of the body.
“Anybody who has been outdoors on a cold day knows that if your hands and your fingers get too cold, you begin to lose a sensation of touch,” he explains. “Your fingertips become almost numb. And it's really that cooling effect that we're seeking to exploit.”
The team created what Rogers describes as a “rubber band” with tiny channels slightly larger than a human hair embedded in it. One side of the 5-millimeter-wide device ends in a cuff-like structure that encircles a nerve. The other comes out of the skin and attaches to a pumping device–similar to how an IV works. Cooling fluid, which boils at a low temperature, is pumped into one of the band’s thin channels to the nerve. It meets up with dry nitrogen that flows through a separate channel, and immediately evaporates, creating a cooling effect. The gas flows back out through a different channel, then recondenses and passes back through the device again, forming a closed loop system. The device is described in a new study published today in Science.
Inside the device is a tiny temperature sensor, so a user can monitor and control the temperature of the nerve by adjusting the flow rate of the coolant. Getting a nerve too cool can result in tissue damage. The temperature sensor is made up of four layers; a layer of magnesium is encapsulated by two layers of silicon dioxide, an insulating material, and a layer below that serves as an adhesive.
“Current can flow through that magnesium layer—it's a metal—and the resistance of that metal changes as a function of temperature,” Rogers explains.
The device is also fully dissolvable in the body, which eliminates the risks involved in surgical removal. The time it takes to dissolve—usually days or weeks—depends on the material used and its thickness. Rogers has created a number of electronic devices that the body can absorb, including a transient pacemaker in 2021. In 2013, he won a Smithsonian magazine American Ingenuity Award for his work.
The researchers tested their device on the sciatic nerve of rats, which carries sensory signals from nerves that terminate in the paws. By applying pressure to the rat paws, they measured how much force was needed to cause the rats to retract their appendages.
“The idea is that as you create a numbing sensation in the paw, you have to push harder and harder in order to create that retraction response,” Rogers says. “So, by cooling the sciatic, we can increase the threshold pressure that you have to apply to the paw by about a factor of ten.”
Right now, Rogers says the next steps are to examine biological aspects of the human body to improve the device’s functionality. Overcooling could lead to nerve damage, so understanding the body’s limitations is crucial.
”After you stop the cooling, how long does it take the nerve to kind of recover so you can restart the cooling?” he says. “Those are the kinds of studies that I think are the most important ones to conduct before using a device with humans.”
John Wood, a neurobiologist at the University College London, is more skeptical of this pain relief method. Wood studies pain pathways, including Nav1.8, which is important in relaying pain signals from nerves throughout the body to the spinal cord.
“I think given the global nature of many chronic pain syndromes, this approach is unappealing,” Wood writes in an email, adding that implantable devices are “problematic.”
Wood says drugs like the Nav1.8 inhibitor from the pharmaceutical company Vertex, which is administered in pill form, have shown strong pain relieving effects in humans. Recently, Vertex announced that VX-548, a Nav1.8 inhibitor, had outperformed a placebo in phase 2 trials for acute pain after two types of surgery.
“This is a much greater advance,” he writes.
Rogers agrees that any implant comes with risks, but his team tried to minimize risks through engineering. The soft, rubber band-like structure, about as thick as a sheet of paper, moves naturally with the muscle tissue surrounding the nerve, and the device’s dissolvability minimizes the risk of damaging the nerve with removal, he says.
The device allows a user to regulate their own pain relief, which Rogers describes as a major benefit.
“It provides all kinds of engineering controls that are absent from any kind of pharmaceutical-based approach and delivered in a very targeted way,” he explains. “So instead of coursing through the entire body, as is the case with many types of pain relief medications, this device is really acting only on the part of the body that's relevant to suppressing the pain sensation.”
Laura Bohn, a biochemist at University of Florida Scripps Biomedical Research, calls the device “novel” and “innovative.” Pain should be approached from multiple angles, she says. “Just as there are very many types of pain, there are very many types of mechanisms to modulate it,” she explains.
Bohn studies how receptors in the body function—including opioid, serotonin and cannabinoid—in the hopes of finding new ways to treat pain and addiction. “The more tools we have, the more opportunities we have to refine therapies,” she adds. “I think everyone's trying to replace opioids, but I personally still think that there's room for opioids when used appropriately. So I think it's another step in building up a toolbox.”
Rogers envisions the device could be used in hospitals for acute pain after surgery. The surgeon would insert the device toward the end of an operation—when a patient is already cut open—and suture the surgical site, leaving the tube coming up through the skin to attach to the pump. The patient would then be tethered to an external pumping apparatus for a period of time.
In the far future, he imagines the system could be adapted in a way that patients could use it in a home setting, though it would require more engineering.
“We're pretty excited, but at the same time, we understand that there's additional work that needs to be done,” he says. “Being able to have a switch to turn on and off pain, I think, would be an amazing thing, and maybe this is one approach to doing that.”