Intra-somatosensory cortical circuits mediating pain-induced analgesia

Abstract

Pain in one part of the body profoundly diminishes the sensation of pain in other parts of the body in humans. Here, we found that pain-related behaviors in hindpaw are inhibited by noxious stimuli from diverse body regions in mice. Using activity-dependent cell labeling in male FosTRAP2 mice, we captured a neuronal ensemble in the layers 2–4 of secondary somatosensory cortex (S2) that was activated during pain at diverse body regions induced analgesia. Single-cell projection analysis showed that these S2 neurons receive projections from the contralateral S2 and specifically innervate the layer 4 of primary somatosensory cortex (S1). Microendoscopic calcium imaging and chemogenetic manipulation in freely moving mice showed that this S2 → S1 feedforward inhibitory circuit mediates ipsilateral pain-induced analgesia, whereas contralateral S2 innervation of the S2 → S1 circuit mediates contralateral pain-induced analgesia. Our study defines the intra-somatosensory cortical circuits underlying “pain inhibiting pain”, expanding the scope of known circuit mechanisms involved in pain relief. Neural mechanisms underlying “pain inhibiting pain” are not fully understood. Here authors show that a neuronal ensemble of the bilateral secondary somatosensory cortex responds to noxious stimulus signals from diverse body regions, and define the intra-somatosensory cortical circuits mediating pain-induced analgesia.