A study published in Nature has identified a neural circuit that may help explain the biological mechanisms behind the placebo effect.
Methods
Researchers from Harvard University and the University of North Carolina at Chapel Hill conditioned mice using two chambers, one with a comfortably warm floor and one with a painfully hot floor, to expect pain relief when entering the previously cooler chamber. They then made both chambers painfully hot and observed the mice's pain-related behaviors.
Live-imaging tools and electrophysiological recordings were used to identify groups of neurons active during the placebo experiment, including the pontine nucleus (Pn) in the brainstem. Transcriptomic analysis revealed that 65% of Pn neurons had opioid receptors.
Results
Blocking Pn neuron activity led to placebo-conditioned mice performing pain-relief behaviors more quickly when moving onto a hot floor that was previously cooler. Mice with activated Pn neurons took longer to lick their paws.
The opioid receptor-containing Pn neurons extended to three areas of the cerebellum. Purkinje cells in the cerebellum also showed increased activity during the placebo experiment.
Conclusion
The study identified a neural circuit involving the brainstem and cerebellum that may play a role in placebo analgesia in mice. Further research is needed to explore the potential implications for human pain treatments and understand the factors that activate the placebo effect in some individuals but not others.
- Naddaf M. How do placebos ease pain? Mouse brain study offers clues. Nature. Published online July 26, 2024. doi:10.1038/d41586-024-02439-w
- Chen C, Qu C, Zelikowsky M, et al. Neural circuit basis of placebo pain relief. Nature. Published online July 24, 2024. doi:10.1038/s41586-024-07816-z