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 have identified a neural mechanism through which sound dulls pain in mice. The findings, which could inform the development of safer methods for treating pain, are published in Science. The study was led by researchers at the National Institute of Dental and Craniofacial Research (NIDCR); China University of Science and Technology, Hefei; and Anhui Medical University, Hefei, China. NIDCR is part of the National Institutes of Health.

“We needed more effective methods to manage acute and chronic pain, and that started with gaining a better understanding of the basic neural processes that regulate pain,” said NIDCR Director Rena D’Souza, DDS, Ph.D. “By uncovering the circuits that mediate the pain-reducing effects of sound in mice, this study adds important knowledge that may ultimately inform new approaches to pain therapy.”

Since the 1960s, human studies have shown that music and other types of sound can help relieve 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, is less clear.

“Human brain imaging studies have implicated certain brain areas in music-induced analgesia, but this is only an association,” said senior co-author Yuanyuan (Kevin) Liu, Ph.D., Stadtman’s proprietary pathway investigator at NIDCR. “In animals, we can further explore and manipulate the circuitry to identify the neural substrates involved.”

The researchers first exposed mice with inflamed paws to three types of sound: pleasant classical music, unpleasant rearrangements of equal parts, and white noise. Surprisingly, all three types of sound, when played at low intensity relative to background noise (around whisper level) reduced pain sensitivity in mice. The higher intensity of the same sound had no effect on the animal’s pain response.

“We were really surprised that it was the intensity of the sound, and not the category or perception of sound pleasure that mattered,” Liu said.

To explore the brain circuitry underlying this effect, the researchers used a non-infectious virus coupled to a fluorescent protein to track relationships 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 pathways with a light and small molecule-based technique mimicked the pain-dull effect of low-intensity noise, while turning on the pathways restored the animals’ sensitivity to pain.

Liu said it was unclear whether similar brain processes were involved in humans, or whether other aspects of sound, such as harmony or perceived pleasure, were important for relieving human pain.

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

The results could provide scientists with a starting point for research to determine whether the animal findings apply to humans, and could ultimately inform the development of safer alternatives to opioids for treating 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 Research Foundation, Anhui Province Natural Science Foundation, and China University of Science and Technology Research Fund of the Double First Class Initiative.

Reference: Zhou W, et al. Sound induces analgesia via the corticothalamic circuit. Science. 7 July 2022.

This press release describes the basic research findings. Basic research improves our understanding of human behavior and biology, which is the basis for advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and gradual process—every research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without a basic knowledge of 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 the nation’s leading funder of oral, dental and craniofacial health research.

About the National Institutes of Health (NIH): NIH, the national medical research institute, includes 27 Institutes and Centers and is a component of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and is investigating causes, treatments, and cures for common and rare diseases.

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Research methods

Experimental study

Research Subject

Animal

Article title

Sound induces analgesia via the corticothalamic circuit

Article Publication Date

7-Jul-2022

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