Neural circuit basis of placebo pain relief, 2024, Chen et al.

Neural circuit basis of placebo pain relief
Chen, Chong; Niehaus, Jesse K.; Dinc, Fatih; Huang, Karen L.; Barnette, Alexander L.; Tassou, Adrien; Shuster, S. Andrew; Wang, Lihua; Lemire, Andrew; Menon, Vilas; Ritola, Kimberly; Hantman, Adam; Zeng, Hongkui; Schnitzer, Mark J.; Scherrer, Grégory

Placebo effects are striking demonstrations of mind-body interactions. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain, a phenomenon known as placebo analgesia. However, despite the strength of placebo effects and their impact on everyday human experience and failure of clinical trials for new therapeutics, the neural circuit basis of placebo effects has remained elusive.

Here, we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACC→Pn), a pre-cerebellar nucleus with no established function in pain. We created a behavioral assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation.

Inhibition of the rACC→Pn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACC→Pn neurons during pain relief expectation, providing cellular-level evidence of a role for the cerebellum in cognitive pain modulation.

These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.

Link | PDF (Nature)

 

Seems like a huge stretch to me to relate this to the placebo effect as observed in clinical studies, which is largely, if not entirely, a problem of accurate measurements, or lack thereof. Or the general idea of whatever it is people mean by placebo.

The Stanford Prison Experiment, no longer at Stanford, with rats. Or, well, actually some of the authors are at Stanford so I guess it's just with rats.

 

Nuff said.