Since the 1960s, human studies have demonstrated music and other kinds of sound could alleviate acute and chronic pain, but the mechanism for why this worked wasn't clearly understood -- until now.

Researchers from the National Institute of Dental and Craniofacial Research (NIDCR), the University of Science and Technology of China, Hefei, and Anhui Medical University, Hefei, China teamed up to explore and manipulate the brain circuitry in mice with regards to sound and pain (Science, July 7, 2022, Vol. 377:6602).

They exposed mice with inflamed paws to three types of sound: a pleasant piece of classical music, an unpleasant rearrangement of the same piece, and white noise. All three types of sound, when played at a low intensity relative to background noise, reduced pain sensitivity in the mice. However, higher intensities of the same sounds didn't affect pain responses.

To determine why, the team then used noninfectious viruses combined with fluorescent proteins to trace connections between brain regions. They spotted a route from the auditory cortex to the thalamus and discovered low-intensity noise reduced the activity of neurons at the receiving end of the pathway in the thalamus.

Not using sound but instead light- and small molecule-based techniques to suppress that neural pathway mimicked the pain-blunting effects of low-intensity noise. Also, turning on the pathway restored pain responses.

It's unclear if similar brain processes are involved in humans or whether other aspects of sound, such as perceived harmony or pleasantness, are important for human pain relief.