Researchers discover how sound reduces pain in mice

News release

Thursday, July 7, 2022

Newly discovered brain circuits may point to more effective pain therapies.

An international team of scientists has identified the neural mechanisms by which sound dulls pain in mice. The findings, which could inform the development of safer pain treatments, were published in Science. The study was led by researchers from the National Institute of Dental and Craniofacial Research (NIDCR); 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 for managing acute and chronic pain, and that starts with gaining a better understanding of the underlying neural processes that regulate pain,” said NIDCR Director Rena D’Souza, DDS, Ph.D. “By revealing the electrical circuit that mediates the pain-relieving effects of sound in mice, this study adds critical knowledge that could ultimately inform new approaches to pain therapy.”

Dating back to the 1960s, human studies have shown that music and other types of sounds can help relieve acute and chronic pain, including pain from dental and medical surgery, childbirth, and cancer. However, how the brain produces this pain reduction, or analgesia, was not as clear.

“Human brain imaging studies have implicated certain brain regions in music-induced analgesia, but these are only associations,” said co-senior author Yuanyuan (Kevin) Liu, Ph.D., a Stadtman Research Fellow at NIDCR. “In animals, we can more fully probe and manipulate the circuits 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 (around whisper level), reduced pain sensitivity in mice. Higher intensities of the same sounds had no effect on the animals’ pain responses.

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

To investigate the brain circuitry underlying this effect, the researchers used non-infectious viruses combined with fluorescent proteins to trace the 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 reduces 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 mimics the pain-blunting effects of low-intensity noise, while turning on the pathway restores the animals’ pain sensitivity.

Liu said it is unclear whether similar brain processes are involved in humans, or whether other aspects of sound, such as perceived harmony or pleasantness, are important in alleviating human pain.

“We don’t know if human music means anything to rodents, but it has very 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 could ultimately inform the development of safer alternatives to opioids for pain treatment.

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 Intelligent Technology, National Natural Science Foundation of China, Science Fund for Creative Research Groups of National Natural Science Foundation of China, CAS Project for Young Scientists in Basic Research , Natural Science Foundation of Anhui Province, and Research Funds of the University of Science and Technology of China from the Double First-Class Initiative.

This press release describes a major study. Basic research increases our understanding of human behavior and biology, which underpins the advancement of new and better ways to prevent, diagnose and treat disease. Science is an unpredictable and gradual process – every scientific study builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without knowledge of fundamental basic research. To learn more about basic research, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.

About the National Institute of Dental and Craniofacial Research: NIDCR is a leading national funder of oral, dental, and craniofacial health research.

For the National Institutes of Health (NIH):NIH, the national agency for medical research, includes 27 institutes and centers and is part of the US Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research and investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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References

Zhou Wu, et al. Sound induces analgesia through corticothalamic circuits. Science. 7 July 2022. DOI: science.org/doi/10.1126/science.abn4663

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