Brain circuits for pain and its treatment

Nicole Mercer Lindsay, Chong Chen, Gadi Gilam, Sean Mackey*, Grégory Scherrer

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations


Pain is a multidimensional experience with sensory-discriminative, affective-motivational, and cognitive-evaluative components. Pain aversiveness is one principal cause of suffering for patients with chronic pain, motivating research and drug development efforts to investigate and modulate neural activity in the brain’s circuits encoding pain unpleasantness. Here, we review progress in understanding the organization of emotion, motivation, cognition, and descending modulation circuits for pain perception. We describe the molecularly defined neuron types that collectively shape pain multidimensionality and its aversive quality. We also review how pharmacological, stimulation, neurofeedback, surgical, and cognitive-behavioral interventions alter activity in these circuits to relieve chronic pain.

Original languageAmerican English
Article numbereabj7360
Pages (from-to)1-21
JournalScience Translational Medicine
Issue number619
StatePublished - 10 Nov 2021

Bibliographical note

Funding Information:
We thank J. Blair for editing the manuscript. We regret that we could not cite numerous important studies given the reference number limit and broad scope of this review article. We encourage readers to also consider the references in the articles we could cite. The authors’ research on the circuits for pain and its treatment is supported by NIH grants (S.M.) R61NS11865, R01NS109450, K24NS126781, (N.M.L.) F32DE030003, (G.S.) R01DA044481, R01NS106301, and R21DA049241. G.S. is a New York Stem Cell Foundation – Robertson Investigator.

Publisher Copyright:
© 2021 The Authors, some rights reserved;


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