An international team of scientists has identified the
neural mechanisms through which sound blunts pain in mice. The findings, which
could inform development of safer methods to treat 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 gaining a better understanding of the basic
neural processes that regulate pain,' said NIDCR Director Rena D'Souza,
D.D.S., 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 for pain therapy.'
Dating back to 1960, studies in humans have shown that music
and other kinds of sound can help alleviate 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
areas of the brain in music-induced analgesia, but these are only
associations,' said co-senior author Yuanyuan (Kevin) Liu, Ph.D., a
Stadtman tenure-track investigator 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, when played 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,
and not the category or perceived pleasantness of sound would matter,' Liu
said.
To explore the brain circuitry underlying this effect, the
researchers used non-infectious viruses coupled 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 the pathway in the thalamus.
In the absence of sound, suppressing the pathway with light-
and small molecule-based techniques mimicked the pain-blunting effects of
low-intensity noise, while turning on the pathway restored animals' sensitivity
to pain.
Liu said it is unclear if 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 means anything to
rodents, but it has many 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 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 Basic Research, Natural Science Foundation
of Anhui Province, and the University of Science and Technology of China
Research Funds of the Double First-Class Initiative.
Resource: Science Daily