A soft, implantable cooling device could provide targeted, on-demand pain relief by directly chilling nerves, blocking the transmission of pain signals across peripheral nerves to the brain.

The concepts and design presented in a new study, published in the July 1 issue of Science, offer a promising path toward creating a class of analgesic devices for long-term, non-opioid pain management, particularly following surgery or amputations.

Pain management is a pressing health issue for many, affecting roughly one in five adults globally. Often, those facing short-term or acute pain, like that experienced after surgery or an injury, for example, turn to opioid pain medication. Although this class of powerful pain killers is highly effective, opioids are also highly addictive, and misuse can lead to dependence and fatal overdose. According to the U.S. Centers for Disease Control and Prevention, deaths from overdoses of prescription opioids exceeded 13,000 in 2021.

This has made the search for effective non-opioid alternatives for pain management an important goal, and several techniques, including the use of non-narcotic medications, electrical stimulation, acupuncture, and cognitive and behavioral therapy, have been explored.

Another such approach to alleviating acute pain is analgesic nerve cooling. Like putting ice on a sore joint or muscle, targeted application of cold temperature directly to nerves can block the conduction of pain signals, providing temporary on-demand relief.

"Temperature has a critical role in biological function," said Jonathan Reeder, an assistant professor at the University of Oregon and the lead author of the study. "As the temperature of a nerve drops, the rate of electrochemical processes that enable conduction of signals through the nerve slow down to the point where transmission of neural signals ceases."

Cooling a nerve to a moderate 15 degrees Celsius (59°F) has been shown to block the transmission of acute pain signals across the peripheral nervous system.

However, current cooling devices such as thermoelectric coolers are bulky, rigid, power-hungry, and produce waste heat, and are therefore not well-suited for interfacing with delicate soft tissues like nerves. They also lack precise control of where and how much cooling is applied, opening the door for unintended temperature-induced tissue damage. According to Reeder, these issues prevent the use of local nerve cooling as a practical approach for temporary pain management.

"An implantable cooling device with on-demand local analgesia will be a game-changer for long-term pain management," Stanford researchers Shan Jiang and Huosong Hong write in a related Science Perspective.

To address this need, Reeder and his colleagues developed a soft, miniaturized and implantable nerve cooling system based on state-of-the-art microfluidic and flexible electronic technologies.

The thin and elastic device, which borrows its design from electrical nerve cuffs used to stimulate or monitor peripheral nerves, wraps around a nerve fiber, forming a close interface between the device and the tissue to facilitate heat transfer.

Encased within the thin ribbon of water-soluble and biocompatible materials, a system of tiny microfluidic channels directs a biocompatible coolant — rapidly chilled through evaporative cooling — throughout the device, providing targeted cooling directly to the nerve. An adjacent embedded thin film temperature sensor provides real-time temperature monitoring and precise control of operating temperatures.

"This localizes the cooling effect to the footprint of the microfluidic channel," down to the millimeter scale, said Reeder.

What's more, since the device is made from biocompatible and bioresorbable materials, it dissolves within the body within a month, reducing unnecessary surgery risk.

Reeder and the researchers tested the device on rat models of neuropathic pain and found that they were able to rapidly and precisely cool peripheral sciatic nerves to provide local and on-demand pain relief in freely moving animals over several weeks after implantation.

"There may be clinical use cases [in humans] for non-opioid management where postoperative pain signals in peripheral nerves are well-defined and where nerves are already isolated and identified," said Reeder. "For example, after amputations, nerve grafts, or spinal decompression surgeries."

However, nerves cannot be cooled indefinitely without resulting in tissue damage.

"An important next step is the development of a dosing and titration schedule for nerve cooling that maximizes analgesic effects without damaging the nerve," said Reeder.

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