Cooling and Melting the Pain Away

A team of scientists from Northwestern University has built a small, soft, flexible implant that offers on-demand pain relief without using drugs. According to the researchers, the device is the first of its kind and could offer a direly needed alternative to opioids and other addictive medications. The implant’s study was published in the July 1 issue of Science.

The biocompatible, water-soluble device wraps around nerves to deliver precise and targeted cooling to numb nerves and block pain signals to the brain. Users can remotely activate the implant with an external pump and increase or decrease intensity as needed. When the device is no longer needed, it absorbs into the body, removing the need for a surgical procedure to extract it.

The researchers anticipate the device will have the most value for patients who undergo routine surgeries or even amputations that usually require post-operative medications. The device can be inserted during the procedure to help manage post-op pain.

“Although opioids are extremely effective, they also are extremely addictive,” Northwestern’s John A. Rogers, who led the device’s development, told the press. “As engineers, we are motivated by the idea of treating pain without drugs—in ways that can be turned on and off instantly, with user control over the intensity of relief. The technology reported here exploits mechanisms that have some similarities to those that cause your fingers to feel numb when cold. Our implant allows that effect to be produced in a programmable way, directly and locally to targeted nerves, even those deep within surrounding soft tissues.”

Rogers is a bioelectronics pioneer and the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery in the McCormick School of Engineering and Northwestern University Feinberg School of Medicine. He also is founding director of the Querrey Simpson Institute for Bioelectronics. Jonathan Reeder, a former postdoctoral fellow in Rogers’ laboratory, is the paper’s first author.

In a similar manner to how evaporating sweat cools the body, the implant contains a liquid coolant that induces evaporation at a sensory nerve’s specific location.

“As you cool down a nerve, the signals that travel through the nerve become slower and slower—eventually stopping completely,” said study coauthor Dr. Matthew MacEwan of Washington University School of Medicine in St. Louis. “We are specifically targeting peripheral nerves, which connect your brain and your spinal cord to the rest of your body. These are the nerves that communicate sensory stimuli, including pain.

By delivering a cooling effect to just one or two targeted nerves, we can effectively modulate pain signals in one specific region of the body.”

Microfluidic channels in the implant help induce the cooling effect. One channel holds perfluoropentane, a liquid coolant already clinically approved as an ultrasound agent and for pressurized inhalers. A second channel holds dry nitrogen, an inert gas. When these flow into a shared chamber, the reaction between the two causes the liquid to quickly evaporate. A tiny integrated sensor monitors the nerve’s temperature to make sure it’s not becoming too cold, which can cause tissue damage.

“Excessive cooling can damage the nerve and the fragile tissues around it,” Rogers said. “The duration and temperature of the cooling must therefore be controlled precisely. By monitoring the temperature at the nerve, the flow rates can be adjusted automatically to set a point that blocks pain in a reversible, safe manner.”

The new device overcomes limitations that experimental cooling therapies and nerve blockers exhibit. Cryotherapies, for example, are injected with a syringe. But instead of targeting specific nerves, the imprecise approach cools large areas of tissue, which may cause tissue damage or inflammation.

Northwestern’s tiny implant is a mere five millimeters wide at its widest point. One end is curled into a cuff that wraps around a nerve, so sutures aren’t needed to attach it.

Its precise targeting spares surrounding regions for unnecessary cooling and its potential resultant side effects.

“You don’t want to inadvertently cool other nerves or the tissues that are unrelated to the nerve transmitting the painful stimuli,” MacEwan said. “We want to block the pain signals, not the nerves that control motor function and enables you to use your hand, for example.”

In 2018, Rogers, MacEwan, and their colleagues demonstrated the world’s first bioresorbable device, an implant that speeds nerve regenerations. In 2021, Rogers and colleagues introduced a transient pacemaker.

All the device’s biocompatible components naturally absorb into biofluids over days or weeks. According to the researchers, they’re harmless—similar to absorbable stitches. The soft, elastic nerve wrap is about the thickness of a sheet of paper and therefore ideal for treating highly sensitive nerves.

“If you think about soft tissues, fragile nerves and a body that’s in constant motion, any interfacing device must have the ability to flex, bend, twist and stretch easily and naturally,” Rogers said. “Furthermore, you would like the device to simply disappear after it is no longer needed, to avoid delicate and risky procedures for surgical removal.”