Newly identified brain circuits may point to more effective pain therapies

Newly identified brain circuits may point to more effective pain therapies

An international team of researchers has determined the neurological pathways via which sound reduces mouse discomfort.

The research was published in Science and may help with the creation of safer ways to alleviate pain.

The National Institute of Dental and Craniofacial Research (NIDCR), the University of Science and Technology of China, Hefei, and Anhui Medical University, all in Hefei, China, were responsible for the study’s direction. The National Institutes of Health includes NIDCR.

Rena D’Souza, D.D.S., Ph.D., director of NIDCR, stated that “we need more efficient means of managing acute and chronic pain, and that starts with having a greater knowledge of the basic brain processes that regulate pain.”

This study provides vital knowledge that could ultimately guide new pain therapy strategies by revealing the circuitry that underlies the pain-reducing benefits of sound in mice.

Human studies dating back to 1960 have demonstrated that music and other types of sound can lessen both acute and persistent pain, including the pain associated with dental and surgical procedures, childbirth, and cancer.

It was less obvious how the brain causes this analgesia, or reduction in pain.

According to co-senior author Yuanyuan (Kevin) Liu, Ph.D., a Stadtman tenure-track investigator at NIDCR, “Human brain imaging studies have implicated particular areas of the brain in music-induced analgesia, but these are simply connections.”

In animals, we may study and control the circuitry more thoroughly to pinpoint the implicated neuronal substrates.

First, the researchers played three different sounds to mice with inflamed paws: a pleasant piece of classical music, an unpleasant reworking of the same piece, and white noise.

Surprisingly, the mice’s sensitivity to pain was decreased by all three types of sound when they were played at a low volume compared to the background noise (about the volume of a whisper).

The responses of animals to pain were unaffected by louder versions of the same noises.

We were astonished to learn that the importance of sound loudness, rather than its type or perceived appeal, Liu said.

The researchers utilized non-infectious viruses combined with fluorescent proteins to map connections between brain areas in order to investigate the brain circuitry underlying this impact.

They discovered a pathway between the auditory cortex, which receives and interprets sound information, and the thalamus, which serves as a relay for sensory messages from the body, including pain.

Low-intensity white noise decreased the activity of neurons in the thalamus at the receiving end of the route in freely moving mice.

When there was no sound, blocking the channel with light- and small-molecule-based methods simulated the pain-diminishing effects of low-intensity noise, while activating the pathway made the animals more sensitive to pain.

According to Liu, it is unknown if similar brain mechanisms operate in humans or whether other facets of music, such its perceived harmony or pleasantness, are significant for relieving human pain.

Human music has many different connotations for humans—you have a lot of emotional components, he said, adding that it’s unknown whether it has any significance for rodents.

The findings may serve as a springboard for further research to ascertain whether the outcomes from animal studies hold true for people, which may help in the eventual development of safer opioid substitutes.

The NIDCR Division of Intramural Research funded this study.

Additionally, funding was provided by the National Natural Science Foundation of China, the CAS Project for Young Scientists in Basic Research, the Natural Science Foundation of Anhui Province, the University of Science and Technology of China Research Funds of the Double First-Class Initiative, the National Key Research and Development Program of China Brain Science and Brain-Like Intelligence Technology, and the National Natural Science Foundation of China.

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