How Your Brain Tricks Pain: Exploring the Brain circuitry behind the Placebo Effect

 

The Placebo effect has long piqued the interest of researchers and medical professionals. It refers to our brain's capacity to reduce symptoms, such pain, even in the absence of active therapy. Numerous clinical investigations have revealed this paradox: patients report feeling better even after receiving ineffective therapies. It has long been a difficulty to figure out how and why this happens. But new research has revealed a crucial discovery that could help unravel the riddle of the placebo effect and open up novel opportunities for treating pain.

In clinical studies, the placebo effect has been a double-edged sword for decades. One the one hand, it shows how the mind may have an impact on one's physical well-being. Conversely, it makes evaluating novel therapies more difficult. Conventional research has demonstrated that patients can get real pain alleviation with placebos, or false medicines or sham interventions, just by making the mistake of thinking they are taking a prescription.

Mapping the Pain Control Pathway

Advances in Neuroscience have offered a novel insight into the neuronal circuitry responsible for the placebo effect. Although the exact neural pathways involved were unknown, it is known for years that specific brain regions are active when a person expects relief from pain. Researchers have discovered a particular circuit that passes through the pons region of the brainstem to link the anterior cingulate cortex (ACC), a part of the front of the brain linked to emotional and cognitive processing, to the cerebellum at the back of the brain. Anticipating pain relief triggers this pathway, which results in a palpable decrease in pain even in the absence of medication. They labeled neurons in the ACC using genetic tagging, observed neural activity using imaging techniques, then controlled individual neurons with light using optogenetics. Unprecedented detail on how the brain converts actual changes in pain perception into the expectation of pain reduction was made possible by these techniques.

The pontine nucleus, a region that was previously unrelated to pain modulation, receives signals from neurons in the ACC, according to the study. Pain thresholds dropped when the expectation of alleviation increased these signals. On the other hand, blocking this route made the placebo effect less pronounced. Moreover, the cerebellum's Purkinje cell activity patterns resembled those of ACC neurons, indicating the cerebellum's role in modulating cognitive discomfort.

For a number of reasons, the identification of this brain circuit is noteworthy. In the first place, it clarifies how the brain interprets the expectation of pain alleviation. Researchers have pinpointed the precise brain areas and their interactions, as well as the manifestations of placebo effects. This information creates new opportunities for therapeutic approaches. It implies, for example, that engaging this route by means of targeted neurostimulation or pharmaceutical interventions may be able to replicate the advantages of the placebo effect, providing pain relief without the need for actual medication.

 

REFERENCES

1.     Chong Chen, Jesse K. Niehaus, Fatih Dinc, Karen L. Huang, Alexander L. Barnette, Adrien Tassou, S. Andrew Shuster, Lihua Wang, Andrew Lemire, Vilas Menon, Kimberly Ritola, Adam Hantman, Hongkui Zeng, Mark J. Schnitzer, Grégory Scherrer. Neural circuit basis of placebo pain relief. Nature, 2024; DOI: 10.1038/s41586-024-07816-z

2.     Cover image - https://cosmosmagazine.com/health/medicine/placebo-effect/