ABOVE: This flexible, dissolving implantable band chilled nerves in rats for pain relief. Northwestern University
For decades, opioids have dominated pain management. But the drugs are frequently ineffective for chronic pain and can lead to addiction, prompting researchers to search for alternative ways to manage pain.
Now, a team of scientists at Northwestern University have developed a miniaturized implant that they say treats pain in rats by simply cooling the peripheral nerves that transmit information between the brain and the rest of the body.
This soft implant, described in a paper published yesterday (June 30) in Science, is made from water-soluble and biocompatible materials that allow it to wrap around peripheral nerves like a cuff. Its unique engineering allows it to target and cool nerves in an area as small as several millimeters, making the device far more effective than other, less precise nerve cooling technologies that can damage the surrounding muscle tissue.
“When your fingers get cold, they get numb. So that’s the basic physiology of what we’re doing,” says study coauthor John Rogers, a materials scientist at Northwestern. “But we’re doing it in a very targeted way: directly applied to nerves deep within soft tissue systems.”
The implant consists of a flexible band containing tiny channels through which the cooling agent perfluoropentane can be pumped via an external system. Another channel contains dry nitrogen. When the perfluoropentane meets with dry nitrogen in a shared chamber, it immediately evaporates and cools the nerves down to 10 °C. The idea is that as the temperature of the nerves drops, so does the intensity and speed of electrical signals moving through them. Eventually, the nerves stop transmitting information, including pain signals. The implant dissolves 20 days after insertion, and is fully excreted by the kidneys 30 days after that, according to the study.
The complete cooling system is analogous to an air-conditioning unit, says Vedran Đerek, a physicist at the University of Zagreb in Croatia, who helped develop a bioelectric stimulator that can be wrapped around peripheral nerves to treat chronic pain. Đerek was not involved in the new study.
To test the device, the researchers poked rats’ paws with a sharp filament and measured the force it took to induce the animals to retract their limbs. Then they used the device to cool the animals’ sciatic nerves, which branch from the lower back down to the legs, and repeated the test.
“What we see is, when we block pain signals through associated peripheral nerves, the force that’s required to induce that retraction increases very substantially,” says Rogers. That suggests that the implantable device is able to block signals normally transmitted through the peripheral nervous system and “eliminate that sensation of pain.” He predicts that the device would work similarly in humans, and could be implanted during amputation or nerve graft surgery to combat pain afterward. However, the device isn’t yet ready for testing in humans.
“It’s very difficult in practice to cool down a nerve in a very localized manner, so this kind of approach is very interesting,” says Đerek.
Steven P. Cohen, an anesthesiologist at the Johns Hopkins University School of Medicine, concurs with the researchers that there’s a need to develop more precise ways of managing nerve pain. “We do neuroleptic procedures [injecting phenol to block nerve pain] all the time, but they’re not really precise,” he explains, since the phenol “could spread to places you don’t want.”
However, according to Cohen, the device might not eliminate the pain associated with phantom limbs, a common problem faced by amputees, since that pain is associated with reorganization that takes place in the brain after a limb is removed.
“There are definitely peripheral mechanisms for pain, but that’s not [the] only one. And it might not even be the main cause,” he adds.
While Rogers agrees it’s conceivable that there are other factors controlling pain intensity besides transmission of signals in the peripheral nerves, such as psychological influences. However, he says “I doubt that it’s significant.”
The next step for Rogers and his team is to fine-tune the specifics of the nerve cooling system in order to strike the balance between cooling a nerve long enough to block pain signals but not long enough to damage the tissue. They also need to determine how much recovery time is needed to reverse the cooling process. As far as the system itself goes, Rogers wants to make the system much more compact, replacing the current benchtop pump with a battery-powered device of his own design that would be “the size of a credit card.”
“The way that we’re doing it now is a reasonable way to deploy the technology in a hospital environment,” he says. “But it would be a lot nicer if you could put [the pump] on your belt and stick it on your skin.”
