Bob Marley once said, "One good thing about music, when it hits you, you feel no pain." A recent study using a mouse model backs up Marley's musing with some scientific data.

In the past, scientists have explored the idea of using music as a therapy in a variety of ways. One study revealed that joining a choir might improve the lives of people with Parkinson's disease, for instance. Other studies have investigated music as a potential treatment for epilepsy.

Others still have concluded that music, in the right setting, can reduce the sensation of pain. For instance, one recent meta-analysis of 14 studies concludes that "music may be beneficial as an adjuvant for chronic pain patients, as it reduces self-reported pain and its common comorbidities."

With the opioid crisis in full flow, finding ways to enhance the effectiveness of less addictive pain medication without producing side effects would be game-changing. A new study reopens the investigation and retests the power of music—in combination with four different medications—against two models of pain in mice. The researchers, from the University of Utah Health in Salt Lake City, have published their findings in the journal Frontiers in Neurology.

Music vs pain

The researchers used two pain models: the carrageenan model, which mimics inflammation-related pain; and plantar incision, which replicates surgical pain.

They split the mice into two groups of five to eight animals. They exposed the control group to only ambient noise, while they played the experimental group three 3-hour segments of Mozart each day for 3 weeks.

Interestingly, the researchers did not choose the segments of music at random. As Grzegorz Bulaj, PhD, an associate professor in medicinal chemistry, explains, "Music is like DNA. We had musicians analyze sequences of several Mozart pieces to optimize the playlist. This was exciting but challenging to integrate these musical analyses into neuropharmacology."

They ran the study four times, each time using a different drug that can reduce pain. These drugs were ibuprofen, cannabidiol, levetiracetam, and a galanin analog called NAX 5055. Both the control and the music groups received doses considered to be suboptimal.

The ibuprofen trials produced the most striking results. In the group that listened to music, pain responses in the carrageenan model dropped by 93%, compared with the mice that took ibuprofen but did not listen to music. Also, in the carrageenan model, music and cannabidiol reduced swelling by 21%. NAX 5055 plus music reduced swelling by 9%. In the surgical pain model, music also significantly reduced some but not all responses to pain.

"There is emerging evidence that music interventions can alleviate pain when administered either alone or in combination with other therapies. I was particularly excited to see reduced swelling in the inflammatory pain model."

—First study author Cameron S. Metcalf, PhD

Metcalf goes on to explain that standard inflammation medications do not produce such a quick response.

Surprises and next steps

Using animal models comes with certain difficulties, but in this case, the scientists' use of a mouse model makes it more interesting; it removes the complex human psychological response to music. One is almost tempted to believe that harmony has an intrinsic healing quality. Although it may seem surprising that a rodent might physiologically respond to music, this is not the first time that scientists have demonstrated this. Research into mice and music has a long pedigree.

For instance, the authors of a review of 42 relevant studies—published in December 2018—found that "[m]usic interventions seem to improve brain structure and neurochemistry, behavior, immunology, and physiology in rodents." Among other things, the authors write that "music exposure was linked with statistically significantly improved spatial and auditory learning, reduced anxiety-related behavior, and increased immune responses."

"The holy grail is to combine the right drug with this new paradigm of music exposure, so we do not need as much drug for analgesic effects."

—Grzegorz Bulaj, PhD

How does music exert its effect?

The scientists did not design this study to unpack how music might reduce pain, but they do outline some theories. For instance, earlier research demonstrated that music upregulates the production of brain-derived neurotrophic factor (BDNF). This protein supports neurons and encourages the growth of neurons and synapses. In the long-term, BDNF inhibits pain sensitivity.

Other theories that the study authors consider are music's ability to impact parasympathetic tone, cortisol levels, pro-inflammatory cytokines, the dopaminergic system, and opioid receptors. It will take a great deal more work to tease apart the mechanisms involved, and the answer is likely to involve all of the above and more.

Much more to learn

It is important to note some of the study's limitations. Firstly, the scientists only used small numbers of animals, so we cannot draw firm conclusions at this stage. Also, the study did not address other types of pain, such as neuropathic pain, which is caused by nerve damage. Another issue is that the scientists only used major key sections of Mozart's music, and, of course, there is a wealth of variation in music. In fact, most studies exploring the physiological impact of music focus on classical music.

Additionally, mice hear different frequencies than humans, and it is unclear how this impacts the results and their relevance to humans. The authors also note limitations in their choice of control group, having exposed the control mice to ambient sound. In future studies, it would be interesting to replace this with total silence, white noise, or a different type of music.

In many ways, the study presents more questions than it answers. What would happen if the mice listened to different styles of music? What if they listened for longer each day? And what if they listened for 6 weeks or 6 months?

However, the results remain highly interesting. As Bulaj points out, "If we could package music and other nonpharmacological therapies into mobile apps and deliver them with drugs and it works, it will be better than drugs alone. It is exciting to find new ways to improve pain treatments."

No doubt, researchers will chase this line of investigation further. Anything that helps reduce pain without adverse effects is of great interest. Perhaps one day, doctors will be able to prescribe a playlist to accompany our pills.