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Saturday, December 10, 2022

How sound reduces pain in mice: Newly identified brain circuits may point to more effective pain treatments

An international team of scientists has identified the neural mechanism through which sound blunts pain in rats. The findings, which could inform the development of safer methods for treating pain, were published in science, The study was led by researchers from 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.

NIDCR Director Raina D’Souza, DDS, Ph.D. “By uncovering the circuitry mediating the pain-reducing effects of sound in rats, this study adds important knowledge that may ultimately inform new approaches to pain therapy.”

Studies in the 1960s have shown that music and other types of sound can help reduce 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 brain regions in music-induced analgesia, but these are only associations,” said co-senior author Yuanyuan (Kevin) Liu, PhD, Stedman tenure-track investigator at the NIDCR. “In animals, we can fully explore and manipulate the circuitry to identify the neural substrates involved.”

The researchers first exposed swollen clawed rats to three types of sound: an enjoyable piece of classical music, an unpleasant rearrangement of the same piece, and white noise. Intriguingly, 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 rats. The high intensity of the same sounds had no effect on the animals’ pain responses.

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

To explore the brain circuitry underlying this effect, the researchers used non-infectious viruses 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 serves as a relay station for sensory signals, including pain, from the body. In freely moving rats, low-intensity white noise reduced the activity of neurons at the 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 effect of low-intensity noise, whereas turning on the pathway restores the animals’ sensitivity to pain.

Liu said it is unclear whether 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.

“We don’t know if human music has any meaning for rodents, but it has many different meanings for 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 eventually 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 was also received from the National Key Research and Development Program of China Brain Science and Brain-Like Intelligence Technology, the National Natural Science Foundation of China, the Science Fund for Creative Research Groups of the National Natural Science Foundation of China, and the CAS Project for Young Scientists. Basic Research, Natural Science Foundation of Anhui Province, and University of Science and Technology of China Research Funds of Double First-Class Initiative.

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