Unlocking the Placebo Effect: How the Brain Self-Tricks for Relief

In a fascinating discovery, scientists have identified what happens in our brains when we expect pain relief but unknowingly receive a placebo instead. This not only confirms the “placebo effect,” but also offers clues about how powerful the mind is in mitigating physiological functions such as pain.

Pain research has struggled with design issues, as even double-blind, randomized trials often show placebo recipients reporting relief from their treatment Until now, scientists did not know exactly what was happening in the brain during these events.

Breakthrough Study on Pain Pathways

A study by UNC School of Medicine, Stanford, Howard Hughes Medical Institute, and Allen Institute for Brain Science revealed a pathway from the cortex to the cerebellum that explains how pain relief can occur without analgesics.

Discovering that neurons in the cortex communicate with the pons and cerebellum to adjust pain thresholds based on expectations is surprising and exciting, said Greg Scherrer from UNC School of Medicine. “This finding opens up possibilities for new pain treatments using drugs or neurostimulation.”

The researchers first identified, through imaging, regions of the brain with increased activity, but it was not clear exactly what was happening—only that something definitely was. From there, they conducted an intricate study on mice to focus on the mechanisms at play.

Mouse Study and Pain Pathway Activation

In the mouse study, researchers found that neurons and synapses along the brain’s pathway—from the cortex to the cerebellum—became highly active when pain relief was expected, regardless of actual medication.

Examining the anterior cingulate cortex (ACC), linked to the placebo effect in pain studies, scientists used various methods, including genetically tagged neurons, calcium imaging, RNA sequencing, electrophysiological recordings, and optogenetics.

Key Discoveries in Pain Modulation

They discovered that when mice received a placebo, the rostral ACC neurons signaled the pontine nucleus, activating other signals along the pathway despite no actual pain relief.

There is an extraordinary abundance of opioid receptors here, supporting a role in pain modulation, Scherrer said. When we inhibited activity in this pathway, we realized we were disrupting placebo analgesia and decreasing pain thresholds. Then, in the absence of placebo conditioning, when we activated this pathway, we caused pain relief.

Confirmation of the Cerebellum’s Role

They found that the large, branch-like Purkinje cells in the cerebellum replicated the activity seen in the initial area of neuronal excitement, in the ACC. This confirmed that the cerebellum had a key role in pain messaging

The findings solve a puzzle for neuroscientists and dispel the notion that the placebo effect is “all in your head.” Researchers believe it could lead to new, effective pain relief approaches, including for chronic disorders.

We need better treatments for chronic pain without harmful side effects and addiction,” Scherrer said. “Our findings may lead to targeting this new neural pain pathway for more effective treatment.”

Read the original article on: New Atlas

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