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 Fos TRAP2 m...

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Main Authors: Ji-Ye Huang, Yu-Xin Jin, Wan-Ying Dong, Wan Zhao, Ping-Kai Cheng, Jun-Hao Miao, An Liu, Di Wang, Juan Li, Zhi Zhang, Wenjuan Tao, Xia Zhu
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57050-y
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Summary: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 Fos TRAP2 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.
ISSN:2041-1723