By Pat Anson, PNN Editor

Wolfgang Amadeus Mozart is widely considered the most gifted and prolific composer in the history of classical music. Mozart composed over 600 symphonies, concertos and operas, and many remain popular two centuries after his death.

Were he alive today, Mozart would probably be flattered to learn that his music is being studied as a pain reliever.  And amused that some of his most devoted listeners are mice.

Music therapy won’t cure chronic pain, but there’s a growing body of evidence that it helps distract and alleviate pain and anxiety. Mozart’s “Sonata for Two Pianos” has been found to be particularly helpful in treating patients with epilepsy.

Researchers at the University of Utah took that theory a step further, to see if music can decrease pain and improve the effectiveness of ibuprofen and cannabidiol (CBD), the non-psychoactive compound found in marijuana.

"We know these drugs work without music but they can produce toxicity and adverse effects," said senior author Grzegorz Bulaj, PhD, an associate professor in medicinal chemistry at University of Utah Health. “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."

‘Music is Like DNA’

Bulaj and his colleagues selected some of Mozart’s compositions and arranged them on a playlist for laboratory mice. That’s right, mice. Humans were not part of the study.

The playlist was made up of two faster-paced allegro sections separated by a slower adagio section — with “Sonata for Two Pianos” played multiple times. The goal was to “balance arousal” and “minimize any potential stress on the mice.”

"Music is like DNA. We had musicians analyze sequences of several Mozart pieces to optimize the playlist," Bulaj said. "This was exciting but challenging to integrate these musical analyses into neuropharmacology."

The mice were divided into two groups (five to eight mice in each group), with a control group exposed to ambient noise, while mice in the music group listened to the Mozart playlist three times a day for 21 days.

Both groups were given ibuprofen, CBD and two epilepsy drugs. The mice received one sub-optimal dose of each drug and then put through a series of inflammatory pain tests in the laboratory.

When combined with music, ibuprofen reduced inflammation in the mice by 93 percent compared to ibuprofen alone. Mice exposed to Mozart and CBD had a 70 percent reduction in inflammation compared to CBD with no music. Researchers say they were unable to evaluate the effectiveness of music with epilepsy drugs.

"There is emerging evidence that music interventions can alleviate pain when administered either alone or in combination with other therapies," said first author Cameron Metcalf, PhD, a research assistant professor in Pharmacology and Toxicology at University of Utah Health. "I was particularly excited to see reduced swelling in the inflammatory pain model."

According to Metcalf, medications currently available to treat inflammation do not show such a robust response. "It is exciting to think of what this might mean for the anti-inflammatory effects of music interventions and where the research may take us next," he said.

Mice hear at different frequencies than humans, and the effect of music volume or duration remains unclear. So is the type of music. Is Mozart a better pain reliever than Beyonce? We don’t know. Also unclear is whether any of these results can be duplicated in people. But Bulaj believes future studies should explore the pairing of music with pain relievers.

"If we could package music and other non-pharmacological therapies into mobile apps and deliver them with drugs and it works, it will be better than drugs alone," Bulaj said. "It is exciting to find new ways to improve pain treatments."

Mozart didn’t need an app or mice to figure that out. “Music, even in situations of the greatest horror, should never be painful to the ear but should flatter and charm it,” he wrote to a friend.

The study findings are published online in the journal Frontiers in Neurology.