Nerve-cooling, dissolving implant offers drug-free pain relief

• Researchers created a rubber band-like device that relieves pain by wrapping around nerves and cooling them down.
• The device reduces pain sensitivity in rat models of sciatic nerve injury, offering a non-opioid alternative for pain relief.
• The researchers say that more research is needed before the device can enter human trials.

Although opioids carry a high risk for abuse, due to their high efficacy in treating pain, they continue to be widely in use.

Research, however, shows that 21- 29% of patients prescribed opioids for chronic pain misuse them. Meanwhile, opioid misuse following surgery occurs in up to 1.8 in every 1,000 people who underwent thoracic and spinal fusion operations.

In 2021, the Centers for Disease Control and Prevention (CDC) recorded an estimated 100,306 drug overdose deaths in the United States from April 2020 to April 2021, up by 28.5% from the previous year.

The development of new non-addictive pain medications could help curb opioid misuse.

Recently, researchers developed a small, biocompatible implant device that wraps around nerves and relieves pain by cooling them down.

“The device physically resembles a rubber band, but with capabilities in cooling targeted regions of peripheral nerves to block the propagation of pain signals,” Dr. John A. Rogers, professor of materials science and engineering, biomedical engineering and neurological surgery at Northwestern University, and lead author of the study, told Medical News Today.

“The materials naturally resorb into the body after a period of use, timed to address [the] pain that patients experience during recovery from a surgical operation,” he said.

The study appears in Science.

How the device works

Studies indicate that local cooling of peripheral nerves to under 15 degrees Celsius blocks neural signaling. Other studies have shown how the effectiveness of nerve cooling can be improved as a potentially non-addictive, reversible method for long-term pain relief.

However, current devices to cool nerves rely on rigid, bulky systems that are unable to provide localized cooling.

In the current study, researchers created a new nerve-cooling device. Resembling a rubber band, it works by wrapping around individual nerves to cool them down.

The device works via microfluidic channels: one containing liquid coolant known as perfluoropentane and another, dry nitrogen, an inert gas. Cooling happens when the liquid and gas flow into a shared chamber, where they react and cause the liquid to evaporate.

All the while, a tiny integrated sensor monitors the temperature of the nerve to ensure it doesn’t get too cold, which could lead to nerve and tissue damage.

As the device is constructed from water-soluble and biocompatible materials, including magnesium and cellulose acetate, once no longer needed, it harmlessly dissolves into the patient’s body, similarly to dissolvable stitches.

Experiments with rats

The researchers tested the device in a freely-moving rat model of sciatic nerve injury.

Cooling nerves from 33 degrees to 4 degrees Celsius over a 15-minute period decreased signal amplitude by 77% and slowed signals by 97%.

Both amplitude and speed of signaling returned to 97% of their initial values after rewarming to body temperature over 3 minutes.

Three weeks following implantation, they found that cooling the nerve from 37 degrees to 10 degrees Celsius led to a sevenfold reduction in the score of the rat’s pain sensitivity.

The researchers reported evidence of bioresorption of the device from histologic analyses after 1, 2, 3, and 6 months of implantation.

The researchers concluded that their nerve cooling device provides a foundation for a class of implantable cooling systems for nonopioid pain management.

They note that it could be particularly useful for post-operative pain and that surgeons could attach the device to affected nerves during the procedure.

Implications for pain management

Dr. Vafi Salmasi, pain medicine assistant professor at Stanford University School of Medicine, who was not involved in the study, told MNT that the new technology has four remarkable advantages that can “certainly change” the treatment of post-operative pain:

• It can be implanted during the surgery with no additional interventions.
• It needs minimal to no maintenance
• It potentially has a very low to no risk of infection
• It is bio-absorbable and does not need to be removed later.

Dr. Kai Yu, senior investigator at the Department of Biomedical Engineering at Carnegie Mellon University, who was also not involved in the study, told MNT that the device and technology were promising.

“Based on these data, this device provides an effective, fast, and precise solution for local and on-demand pain relief, which is certainly non-addictive and promising to replace the postoperative opioid therapy in some scenarios.”
— Dr. Kai Yu

He added that while he is very excited about the work, its successful application “relies on clear anatomy of isolated nerves that are responsible for transmitting pain signals.”

The device is thus limited for post-operative pain from surgeries that involve direct nerve exposure.

“It is still a grand challenge to better manage acute and chronic pain that is not local, or not well defined in the nervous system. Many types of pain show such features,” explained Dr. Yu.

Dr. Rogers noted that while the engineering aspects of the device are complete, it is still in the early stages of development.

“We are now focusing more of our attention on long-term effects of the cooling on the nerves through additional animal model studies. We hope, in several years, to begin evaluations in humans,” he said.

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