Researchers discover how sound reduces pain in mice

Image: Sound reduces pain in mice by decreasing the activity of neurons in the brain’s auditory cortex (green and magenta) that project to the thalamus.
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Credit: Wenjie Zhou

An international team of scientists has identified the neural mechanisms by which sound dulls pain in mice. The findings, which could contribute to the development of safer methods of treating pain, were published in Science† The study was led by researchers at the National Institute of Dental and Craniofacial Research (NIDCR); the University of Science and Technology of China, Hefei; and Anhui Medical University, Hefei, China. NIDCR is part of the National Institutes of Health.

“We need more effective methods of managing acute and chronic pain, and that starts with a better understanding of the basal neural processes that regulate pain,” said NIDCR Director Rena D’Souza, DDS, Ph.D. “By uncovering the circuitry that mediates the pain-reducing effects of sound in mice, this study adds critical knowledge that could ultimately inform new approaches to pain therapy.”

Human studies dating back to the 1960s have shown that music and other types of sound can help relieve acute and chronic pain, including pain from dental and medical surgery, childbirth, and cancer. However, how the brain produces this pain relief or analgesia was less clear.

“Human brain imaging studies have implicated certain areas of the brain in music-induced analgesia, but these are just associations,” said co-senior author Yuanyuan (Kevin) Liu, Ph.D., a Stadtman tenure-track researcher at NIDCR. “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 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, not the category or perceived pleasantness of sound, would matter,” Liu said.

To investigate the brain circuitry underlying this effect, the researchers used non-infectious viruses in combination with fluorescent proteins to trace connections between brain regions. They identified a pathway 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 pad with light- and small-molecule techniques mimicked the pain-attenuating effects of low-intensity noise, while turning on the pad restored the animals’ sensitivity to pain.

Liu said it’s unclear whether similar brain processes are involved in humans, or whether other aspects of sound, such as the perceived harmony or pleasantness, are important for human pain relief.

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

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

This research was supported by the NIDCR Division of Intramural Research. Support also came from the National Key Research and Development Program of China Brain Science and Brain-Like Intelligence Technology, National Natural Science Foundation of China, Science Fund for Creative Research Groups of the National Natural Science Foundation of China, CAS Project for Young Scientists in Basic Research, Natural Science Foundation of Anhui Province and University of Science and Technology of China Research Funds of the Double First-Class Initiative.

References: Zhou W, et alSound induces analgesia through corticothalamic circuits. Science. July 7, 2022.

This press release describes a fundamental research finding. Fundamental research advances our understanding of human behavior and biology, which is fundamental to developing new and better ways to prevent, diagnose and treat disease. Science is an unpredictable and incremental process – any research progress builds on previous discoveries, often in unexpected ways. Most clinical progress would not be possible without the knowledge of basic fundamental research. For more information on basic research, visit:

About the National Institute of Dental and Craniofacial Research: NIDCR is the nation’s largest funder of oral, dental and craniofacial health research.

About the National Institutes of Health (NIH)NIH, the nation’s medical research agency, comprises 27 institutes and centers and is a part of the United States Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, investigating the causes, treatments, and cures for both common and rare diseases.

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