Neocortical circuits in pain and pain relief

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. Neocortical circuits imparting specificity and causality to pain are not well understood. In this Review, Kuner and Tan discuss new insights into the contributions of diverse cerebral domains, their connectivity and their plasticity to the sensory and emotional aspects of pain.