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Neocortical circuits in pain and pain relief

Abstract

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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Fig. 1: The PL cortex.
Fig. 2: Overview of major neocortical circuits and their known efferent pathways that modulate nociception (in black) and negative affective states (in red) in acute and chronic pain.
Fig. 3: Overview of neocortical structures and their known efferent pathways that serve as targets of pharmacological analgesics as well as neurostimulation and neuromodulation/cognitive therapies in chronic pain.

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Acknowledgements

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.

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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.

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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

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