More than 50 million people in the United States are living with chronic pain—about 20% of American adults—according to the Centers for Disease Control and Prevention.
Treatment options range from massage and acupuncture to steroid injections and surgery, but no solution works for everyone because not all pain is the same. In addition, one of the most-used pain treatments, opioids, have addictive properties that have caused a nationwide crisis.
A new study with mice offers what could be an ideal solution—a treatment that does not involve drugs, invasive procedures, or side effects: treating pain with sound.
The discovery was made by an international team of researchers from the National Institute of Dental and Craniofacial Research in the U.S. and the University of Science and Technology of China and Anhui Medical University in Hefei, China.
It’s not the first time sound has been explored as a way to reduce pain. As far back as the 1960s, music and other types of soothing sound have been used to help relieve both acute and chronic pain, but the mechanism by which sound works to mitigate pain was not fully understood.
Brain scans in humans have shown a correlation between pain-relieving sound and certain areas of the brain. To more closely examine the connection, the team exposed mice to three types of sound: soothing classical music, an unpleasant rearrangement of the same piece, and white noise.
They then induced inflammation in the paws of the mice and prodded their paws to test them for pain reactions. They were surprised to discover that all three types of sound reduced the pain sensitivity of the mice when played at low levels. Increasing the volume of the sound also increased their pain responses, indicating that the low level of the sound, slightly louder than background noise at about the level of a whisper, is an important aspect of its effect on pain.
To determine exactly what was happening in the brains of the mice during the pain-numbing effect, researchers repeated the experiment, but this time used fluorescent dye to trace the brain circuitry of the mice. They identified a pathway from the mice’s auditory cortex, which processes sounds, to the thalamus, which acts as a switchboard for sensory signals from the body.
When the mice were exposed to the low-intensity sound, the identified pathway saw reduced neuron activity. To further test the effect, the team used light to block the pathway, and were able to mimic the pain-reducing effect.
The next step is to test the process on humans. While researchers can’t use the same invasive method used on the mice, they can play sounds and track subjects’ brain and thalamus activity using MRI scans to determine if the sounds have the same effect.
While the ultimate goal is to translate the findings to humans, the experiment may actually be beneficial for lab animals as well, by giving researchers a way to reduce the pain the animals experience without affecting research results.
A Genetic Target for Chronic Pain
Researchers at Oxford University made a different discovery in the area of pain management—in a recent mouse study, the team identified a gene that affects sensitivity to pain by changing pain signals in the spinal cord.
The gene, called NCX3, was identified through the genetic sampling of 1,000 human volunteers to see if there were any common genetic variants among people who experience a greater sensitivity to pain.
To better understand the role of NCX3 in pain response, the team conducted a series of experiments in mice. They discovered that an absence of NCX3 resulted in neurons in the spinal cord producing a stronger reaction to pain signals. When the levels of NCX3 in the spinal cord were increased, the mice showed reduced pain responses.
The discovery could be used to develop new drugs for humans that reduce pain by increasing the presence of NCX3.
A New Implant for Pain
With opioids carrying a high risk of abuse, one research team is looking at a type of pain treatment that doesn’t involve drugs at all.
Scientists at Northwestern University have developed a small implant device that wraps around nerves and cools them down, which reduces pain by blocking pain signals. The implant is designed to be temporary, and breaks down naturally in the body after a certain period, making the implant an excellent solution for short-term pain after an injury or operation.
Nerve-cooling has been used in the past, but the systems are large, bulky, and inefficient at targeting specific nerves. The new implant is similar to a rubber band and can wrap around individual nerves and cool them down using the combination of the liquid coolant perfluoropentane and dry nitrogen. The implant includes a temperature sensor to ensure the nerve does not get too cold, which could lead to permanent damage.
The implant was tested in rat models of sciatic nerve injury. Three weeks after implantation of the device and cooling nerves to 10 degrees Celsius, the rats displayed a sevenfold reduction in pain sensitivity.
The team is now testing longer-term nerve cooling in different animal models, and hopes to eventually expand the experiment to humans.
With scientists around the world discovering new ways to treat pain in animal models, there is a hope that humans will soon have safer, more effective treatments for many different kinds of pain.
