Scientists have identified a pathway in the brains of mice that could explain why a placebo, an intervention scientifically proven to have no therapeutic effect, continues to reduce pain. The development of drugs that target this brain pathway may in the future lead to the development of safer alternatives to pain medications, such as opioids or narcotic pain relievers.
If someone unknowingly takes a sugar pill instead of a painkiller, they will still feel better. This phenomenon, known as the “placebo effect”, is a well-known phenomenon and refers to a treatment method that reduces pain symptoms by meeting people’s expectations, even without receiving effective treatment. “Our brains can independently solve the problem of pain based on the expectation that a drug or treatment might have worked,” says Gregory Scherer of the University of North Carolina at Chapel Hill.
To understand how placebo works in the brain, Scherer and his colleagues recreated this effect using 10 mice in a two-chamber cage. One of the chambers had a hot surface, while the other did not. After three days, the animals learned how to relieve their pain in the second compartment.
Then, the researchers injected the rodents with a molecule that caused the active neurons in their brains to glow under the microscope. They put the rats back in the cage again, but this time they heated both chambers.
The brain can relieve pain based on its expectation of the drug’s effect
Both chambers were equally warm; However, the animals still preferred the second compartment and showed fewer signs of pain, such as paw licking, in the second compartment. Also, more activity was observed in the neurons of the cingulate cortex of the mice (an area involved in pain processing), compared to the nine mice that were not conditioned with pain relief in the second chamber.
Further experiments showed that there is a pathway in the brains of mice that connects pain processing neurons to cells in the pontine nucleus and cerebellum; These two brain regions had no previously known role in pain relief.
The researchers used a technique called optogenetics to confirm pain relief by the newly discovered brain pathway. Using this technique, cells can be activated or deactivated by light. This technique allowed the researchers to activate the newly discovered neural pathway in a separate group of mice placed on the hot surface. On average, these animals paused three times longer before licking their paws than mice whose circuits were not activated, meaning they felt less pain.
If the discovered neural pathway does indeed explain the placebo effect, “new strategies will emerge in the evolution of drug discovery,” according to Luana Koloka of the University of Maryland. “If we have drugs that activate the placebo effect in the brain, we have a wonderful strategy for pain management,” he adds.
Scherer also says: “Obviously, the experience of the placebo effect in humans is far more complex than in animals.” However, he still believes that the findings can be generalized to humans because the pain pathways in the brains of rodents and humans are very similar.
The findings of the study have been published in the journal Nature.
