The sensory, associative and limbic neocortical structures play a critical role in shaping incoming noxious inputs to generate variable pain perceptions. Technological advances in tracing circuitry and interrogation of pathways and complex behaviours are now yielding critical knowledge of neocortical circuits, cellular contributions and causal relationships between pain perception and its abnormalities in chronic pain. Emerging insights into neocortical pain processing suggest the existence of neocortical causality and specificity for pain at the level of subdomains, circuits and cellular entities and the activity patterns they encode. These mechanisms provide opportunities for therapeutic intervention for improved pain management.
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The authors thank all members of their laboratory as well as scientists in the Heidelberg Pain Consortium (CRC1158 of the Deutsche Forschungsgemeinschaft) for thought-provoking discussions and expert viewpoints. The authors acknowledge funding to R.K. from the Deutsche Forschungsgemeinschaft in the form of grants for Collaborative Research Centre 1158 (projects B01 and B06) and from the Baden-Württemberg Foundation (Internationale Spitzenforschung; BWST-ISF2017-069). L.L.T. was partially supported by a postdoctoral fellowship from the European Molecular Biology Organization. R.K. is a member of the Molecular Medicine Partnership Unit in the Medical Faculty in Heidelberg and the European Molecular Biology Laboratory.
Nature Reviews Neuroscience thanks Elizabeth May, who co-reviewed with Markus Ploner; Patrick Sheets; and Gregory Scherrer for their contribution to the peer review of this work.
The authors declare no competing interests.
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- Multivariate pattern analysis
A set of tools that can analyse and identify neural responses in the brain as spatially distributed patterns of activity.
- Machine learning
The use of computer algorithms to learn, analyse, identify and predict patterns from data sets with minimal human supervision.
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Tan, L.L., Kuner, R. Neocortical circuits in pain and pain relief. Nat Rev Neurosci 22, 458–471 (2021). https://doi.org/10.1038/s41583-021-00468-2