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Newly Discovered Brain Circuits May Point to More Effective Pain Treatments – ScienceDaily


An international team of scientists has identified the neural mechanisms by which sound dulls pain in mice. The findings, which could help develop 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 treatments for acute and chronic pain, and that starts with a better understanding of the underlying neural processes that regulate pain,” said NIDCR Director Rena D’Souza, DDS, Ph.D. “By identifying the circuit that mediates the analgesic effects of sound in mice, this study adds important knowledge that may eventually inform new approaches to pain therapy.”

Human studies since 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 reduction or analgesia has been less clear.

“Human brain imaging studies have shown that certain brain regions are involved 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 explore and manipulate circuits to identify the neural substrates involved.”

The researchers first exposed mice with inflamed paws to three types of sounds: pleasant classical music, an unpleasant rearrangement of the same piece, and white noise. Surprisingly, all three types of sound, when played at a low intensity compared to background noise (about a whisper level), reduced pain sensitivity in the mice. A higher intensity of the same sounds had no effect on the animals’ pain responses.

“We were very surprised that the intensity of the sound, rather than the category or perceived pleasantness of the sound, would make a difference,” Liu said.

To study 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 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 a pathway in the thalamus.

In the absence of sound, suppression of the pathway using light and small molecule techniques mimicked the pain blunting of low-intensity noise, while enabling the pathway restored the animals’ pain sensitivity.

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

“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 findings could give scientists a starting point for research to determine whether the animal findings apply to humans, and could eventually lead to the development of safer alternatives to opioids for pain management.

This research was supported by the NIDCR Division of Intramural Research. Support was also provided by the National Key Research and Development Program of China Brain Science and Brain-like Intelligence Technology, the National Natural Science Foundation of China, the Scientific Fund for Creative Research Groups of the National Natural Science Foundation of China, the CAS Project for Young Scientists in Basic Research, the Provincial Natural Science Foundation Anhui and the Research Foundations of the University of Science and Technology of China under the Double First Class initiative.

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