An international team of scientists has identified the neural mechanisms by which sound mitigates pain in mice. The results, which could serve to develop safer methods to treat pain, are published in “Science”.
“We need more effective methods to treat acute and chronic pain, and that starts with a better understanding of the basic neural processes that regulate pain,” said the director of the NIDCRDr. Rena D’Souza. “By uncovering the circuitry that mediates the pain-reducing effects of sound in mice, this study adds key insights that could ultimately inform new approaches to pain therapy.”
Since 1960human studies have shown that music and other types of sound They 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 less clear.
We were very surprised that the intensity of the sound, and not the category or perceived pleasantness of the sound, was important.
“Human brain imaging studies have implicated certain brain areas in music-induced analgesia, but these are only associations,” explains co-author Yuanyuan (Kevin) Liu, Stadtman senior fellow 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 swollen 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 sounds, when played at low intensity relative to background noise (approximately whisper level), reduced pain sensitivity in mice. Higher intensities of the same sounds had no effect on the animals’ pain responses.
“We were very surprised that the intensity of the sound, and not the category or perceived pleasantness of the sound, was important,” Liu said.
To explore the brain circuits underlying this effect, the researchers used non-infectious virus coupled to 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 reduced the activity of neurons from the receiving end of the pathway in the thalamus.
In the absence of sound, suppression of the pathway with light- and small-molecule-based techniques mimicked the pain-attenuating effects of low-level noise, while activation of the pathway restored the animals’ sensitivity to pain.
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 to treat pain.
Liu notes that it’s not clear whether similar brain processes exist in humans, or whether other aspects of sound, such as its perception of harmony or pleasure, 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 – it has 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 to treat pain.