“Ice”: This is the old common-sense advice for quick pain relief. As effective as it is, this low-tech treatment is limited by volume and imprecision. But this seemingly crude solution now shows potential as an alternative to opioids and other pain relievers. This alternative comes in the form of an implantable device—Ultra-miniaturized ice pack Apply directly to a single nerve. The device, implanted in rats, produced pain relief, suggesting it could be used to treat post-operative pain or other forms of localized pain in people.
“We know that cooling has great healing power,” says neuroscientist Theanne Griffith of the University of California, Davis, who was not involved in the work. “It has been used to treat pain for centuries.”
The idea of implantable cooling devices is not new, but existing devices are large and bulky. They damage tissue and need to be surgically removed. The new device, designed by Northwestern University researchers and colleagues, is made of a soft, stretchy nerve-like material called poly(octanediol citrate), or POC. A few weeks after implantation, the soluble material simply melts into the body. “Topical cooling is an effective analgesic,” Griffith said. “Conceptually, this shows that you can apply this long-standing knowledge in a really innovative way.” The study, co-led by Northwestern’s John Rogers, was published in science June 30.
The system combines microfluidics (miniature serpentine tubes through which liquids flow) with an electronic interface to measure and control temperature via a remote control, thereby controlling neural activity, and perhaps one day, patients can adjust the settings. The cooling comes from a chemical contained in the tube called perfluoropentane (PFP), which has been approved for biomedical use as an ultrasound contrast agent. Another compartment contains dry nitrogen. When these two chemicals meet, they produce the desired chill. The device is only a few millimeters long and wraps around a small section of a nerve like a cuff, cooling it directly. A second surgery may not be necessary to remove the device, as it dissolves in the body later.
The researchers implanted the device around the sciatic nerve in rats to test its analgesic potential. It rapidly cooled to 5 degrees Celsius, effectively blocking the signals from the nerves, which resumed upon reheating. The researchers then tested the device in rats without nerve injury (SNI), an animal model of chronic pain that damages but does not kill nerves. Three weeks after SNI surgery, two control rats showed greater sensitivity from poke to paw. The damaged nerves were “treated” and cooled to 10 degrees Celsius in three rats that received cooling cuff implants as part of the SNI procedure. This increased the pain sensitivity threshold sevenfold, bringing it back to preoperative levels.
“This approach is cool — no pun intended,” said Alan Basbaum, a pain researcher at the University of California, San Francisco, who was also not involved in the study. “It’s provocative; it’s really interesting. But there are still many questions about its utility in a clinical setting.”
These tests in rodents require further study, the researchers said, because the processed nerve bundles contain nerve cells that carry not only pain but other senses, as well as signals transmitted by motor and sympathetic nerves. If all of these nerves are suppressed, that can have consequences such as numbness (which people report is very unpleasant) or motor weakness. “When you cool the whole nerve, a lot of things happen,” Basbaum said.
“On the plus side, most, if not all, neuropathic pain is driven by abnormal neural activity,” he added, referring to the type of pain caused by nerve damage. “And local anaesthetics are very effective. So in theory, if you cool the nerve to the point that it blocks all conduction, you’re actually doing what the local anaesthetic does.”
“My big problem [is] “What the hell does that mouse feel like?” Pain relief? numbness? “It’s going to impact how it’s used on people,” Griffith said. More sophisticated behavioral tests in rodents are needed to answer these questions. “Human pain is complex; it’s not just the initial [nerve] signal,” Griffith added. “There is a central [nervous system] processing, emotional processing. It would be great to see analytics that enable higher levels of pain perception. “
Co-author of the new study, Matthew MacEwan of Washington University in St. Louis, says the rationale behind the device lies in an “interesting property” exhibited by mammalian nerves: the fact that their level of function depends on temperature. When cooled enough, the nerve stops firing. That’s exactly what Rogers, MacEwan and their colleagues were looking for. “We wanted to find a way to provide gentle nerve cooling as a means of shutting down and blocking painful stimuli,” he said.
The study’s authors suggest that the device could be implanted in the body during procedures that already involve specific nerves, such as amputations, which often result in a painful condition called phantom limb pain. But MacEwan also envisions using it for more common procedures, such as knee replacements.
Security issues still need to be explored. Over time, hypothermia can cause damage to nerves. “We didn’t see any detrimental effects on the nerve fibers,” MacEwan said, “but this is an area we want to explore further — extending the cooling time and ensuring delivery is safe and reversible.”
Griffith added: “You’ll want to see how much cooling we can provide before we damage the nerve. I’m not sure, but five degrees [C] very cold. “
The technology, while promising, needs further development to understand its potential side effects and how it can be used for other applications, Basbaum said. “We haven’t,” he said. “It’s not replacing morphine.”