Tiny implantable cooling device promises drug-free pain relief

A soft, miniaturized bioresorbable implant that delivers focused, minimally invasive cooling power in living tissues can help alleviate pain on demand without the use of medications and may provide an alternative to opioids and other highly addictive painkillers.

Developed by a team of researchers from the Northwestern University in Evanston, Illinois, US, the device is designed to softly wrap around nerves and administer a targeted cooling effect, which, in effect, numbs the nerves and cuts out pain signals to the brain. [Science 2022;377:109-115]

“Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries,” according to the researchers.

The current device, on the other hand, is like a strip of tape that is flexible and as thick as a sheet of paper, measuring just 5 mm at its widest point. The device borrows the design of an electrical nerve cuff but instead of electrical wires, it has a microfluidic channel that carries a microlitre volume of bioinert coolant.

With the device using evaporation—or liquid-to-gas phase transition—as the cooling mechanism, the liquid coolant is then induced to evaporate at the specific location of a nerve.

“As you cool down a nerve, the signals that travel through the nerve become slower and slower, eventually stopping completely,” explained study coauthor Dr Matthew MacEwan, from Washington University School of Medicine in St. Louis, US, in a statement.

“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,” MacEwan continued.

To ensure that the nerve does not get too cold and cause tissue damage, the device integrates a small sensor that allows real-time temperature monitoring.

“Excessive cooling can damage the nerve and the fragile tissues around it, [so] the duration and temperature of the cooling must therefore be controlled precisely,” said Northwestern University’s Prof John Rogers who led the development of the device. “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.”

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

In multiweek in vivo trials, Rogers and MacEwan, along with the rest of their team, have been able to demonstrate the device’s ability to rapidly and precisely cool specific peripheral nerves to provide local, on-demand pain relief in rat models for neuropathic pain.

Finally, all the components of the device use biocompatible materials that naturally dissolve into the body over the course of days or weeks, avoiding the need for surgical extraction. These bioresorbable materials are similar to absorbable stitches and are completely safe.

“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. Furthermore, you would like the device to simply disappear after it is no longer needed, to avoid delicate and risky procedures for surgical removal,” according to Rogers.

The researchers believe that the cooling device is a promising alternative to extremely addictive opioids for treating pain.

“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 said.