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.
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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.
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