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Neural circuit basis of placebo pain relief.
- Source :
-
Nature [Nature] 2024 Aug; Vol. 632 (8027), pp. 1092-1100. Date of Electronic Publication: 2024 Jul 24. - Publication Year :
- 2024
-
Abstract
- Placebo effects are notable demonstrations of mind-body interactions <superscript>1,2</superscript> . 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 <superscript>3-6</superscript> . However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics <superscript>7</superscript> , the neural circuit basis of placebo effects has remained unclear. 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 precerebellar nucleus with no established function in pain. We created a behavioural 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 for a role of 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Female
Male
Mice
Analgesia
Anticipation, Psychological physiology
Calcium Signaling
Cerebellum cytology
Cerebellum physiology
Cognition physiology
Electrophysiology
Gene Expression Profiling
Gyrus Cinguli cytology
Gyrus Cinguli physiology
Mice, Inbred C57BL
Neurons physiology
Pain Management methods
Pain Management psychology
Pain Management trends
Pain Threshold physiology
Pain Threshold psychology
Pons cytology
Pons physiology
Prefrontal Cortex cytology
Prefrontal Cortex physiology
Purkinje Cells physiology
Receptors, Opioid metabolism
Synaptic Transmission
Neural Pathways
Pain physiopathology
Pain prevention & control
Pain psychology
Pain Perception physiology
Placebo Effect
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 632
- Issue :
- 8027
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 39048016
- Full Text :
- https://doi.org/10.1038/s41586-024-07816-z