Novel Pain Management Approach Uses Spearmint to Trigger Pain Relief

In a first-of-its-kind study, researchers reprogrammed cells to shut down pain receptors when the patient is exposed to the scent of spearmint.

Martin Fussenegger, PhD

Researchers have developed a novel strategy that could usher in a new era of pain management and combat the persistent problem of painkiller addiction.

A new study highlighted a bioengineering-based method that involves engineering cells that can target pain receptors and then tie those cells to an aroma-based triggering mechanism. “Our proof-of-principle findings indicate that therapies based on engineered cells can achieve robust, tunable and on-demand analgesia for the long-term management of chronic pain,” the study authors wrote.

The strategy works in a number of steps. First, researchers created “microencapsulated human designer cells” that produce Huwentoxin-IV, a potent analgesic peptide that selectively shuts down a pain-triggering sodium channel called Nav1.7. Next, they rewired an olfactory receptor, OR1A1, so that it induced the expression of a variant of Huwentoxin-IV. The researchers chose an olfactory receptor that is responsive to R-carvone, a chemical that smells like spearmint.

Thus, the researchers created a mechanism in which the smell of spearmint leads to the production of Huwentoxin-IV, which in turn eliminates pain. The so-called “AromaCells” were tested in mouse models, and the results suggested the mice achieved significant and lasting pain relief with exposed to spearmint.

Martin Fussenegger, PhD, the lead author and a professor in the Department of Biosystems Science and Bioengineering at ETH Zurich (Swiss Federal Institute of Technology, Zurich), said the system circumvents one of the key problems associated with pain management.

“The major problem of pain treatment is addiction [to things like morphine, etc.],” he told MD Magazine. “More and more people suffer from pain, and there are no new treatment strategies. Our strategy pioneers a new concept in this sector, which has not seen much progress in the past.”

The study comes at a time of intense focus in the United States on the addictive properties of opioids. US President Donald Trump has declared opioid addiction to be a national “health emergency.”

A number of studies have been published in recent months looking at alternatives to opioids, but this study represents a completely new approach, the researchers wrote.

Fussenegger said he and his team specifically tested for signs of addiction in the mice but found none. On the other hand, mice who were treated for pain with tramadol and morphine exhibited signs of withdrawal once the treatments were stopped.

The advantage of his system is that it specifically targets pain and doesn’t produce the sensation of pleasure. “The protein we express is directly interacting with the major pain receptor, so pain is directly and specifically shut off,” Fussenegger said.

The strategy is still in its infancy, but it could suggest a way forward for chronic pain treatment, and possibly other clinical indications. Fussenegger is enthusiastic in his belief that they may be ushering in a new paradigm in the management of chronic pain.

“This is great news for pain sufferers,” he said. “So far, any therapy was associated with addiction—this is not the case here.”

The study, “Treatment of chronic pain by designer cells controlled by spearmint aromatherapy,” was published in Nature Biomedical Engineering.

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