Scientists Identify Neural Mechanisms Through Which Sound Induces Analgesia in Mice

by johnsmith

Sound, including music and noise, can relieve pain in humans, but the underlying neural mechanisms are unknown. In new research, scientists from the United States and China used a range of methods to demonstrate in mice that the auditory cortex is functionally connected to regions involved in nociception, the sensory process that provides the signals that lead to pain. Their results appear in the journal Science.

Zhou et al. discovered sound reduces pain in mice by lowering the activity of neurons in the brain’s auditory cortex (green and magenta) that project to the thalamus. Image credit: Wenjie Zhou.

Dating back to 1960, studies in humans have shown that music and other kinds of sound can help alleviate acute and chronic pain, including pain from dental and medical surgery, labor and delivery, and cancer.

However, how the brain produces this pain reduction, or analgesia, was less clear.

“Human brain imaging studies have implicated certain areas of the brain in music-induced analgesia, but these are only associations,” said Dr. Yuanyuan Liu, a researcher at the National Institute of Dental and Craniofacial Research.

“In animals, we can more fully explore and manipulate the circuitry to identify the neural substrates involved.”

The researchers first 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.

Surprisingly, all three types of sound, when played at a low intensity relative to background noise (about the level of a whisper) reduced pain sensitivity in the mice.

Higher intensities of the same sounds had no effect on animals’ pain responses.

“We were really surprised that the intensity of sound, and not the category or perceived pleasantness of sound would matter,” Dr. Liu said.

To explore the brain circuitry underlying this effect, the scientists used non-infectious viruses coupled with fluorescent proteins to trace connections between brain regions.

They identified a route from the auditory cortex, which receives and processes information about sound, to the thalamus, which acts as a relay station for sensory signals, including pain, from the body.

In freely moving mice, low-intensity white noise reduced the activity of neurons at the receiving end of the pathway in the thalamus.

In the absence of sound, suppressing the pathway with light- and small molecule-based techniques mimicked the pain-blunting effects of low-intensity noise, while turning on the pathway restored animals’ sensitivity to pain.

“It is unclear if similar brain processes are involved in humans, or whether other aspects of sound, such as its perceived harmony or pleasantness, are important for human pain relief,” Dr. Liu said.

“We don’t know if human music means anything to rodents, but it has many different meanings to humans — you have a lot of emotional components.”

The results could give scientists a starting point for studies to determine whether the animal findings apply to humans, and ultimately could inform development of safer alternatives to opioids for treating pain.


Wenjie Zhou et al. 2022. Sound induces analgesia through corticothalamic circuits. Science 377 (6602): 198-204; doi: 10.1126/science.abn4663

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