Midbrain glutamatergic circuit mechanism of resilience to socially transferred allodynia in male mice

Yi Han, Lin Ai, Lingzhen Song, Yu Zhou, Dandan Chen, Sha Sha, Ran Ji, Qize Li, Qingyang Bu, Xiangyu Pan, Xiaojing Zhai, Mengqiao Cui, Jiawen Duan, Junxia Yang, Dipesh Chaudhury, Ankang Hu, He Liu, Ming Hu Han, Jun Li Cao, Hongxing Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

The potential brain mechanism underlying resilience to socially transferred allodynia remains unknown. Here, we utilize a well-established socially transferred allodynia paradigm to segregate male mice into pain-susceptible and pain-resilient subgroups. Brain screening results show that ventral tegmental area glutamatergic neurons are selectively activated in pain-resilient mice as compared to control and pain-susceptible mice. Chemogenetic manipulations demonstrate that activation and inhibition of ventral tegmental area glutamatergic neurons bi-directionally regulate resilience to socially transferred allodynia. Moreover, ventral tegmental area glutamatergic neurons that project specifically to the nucleus accumbens shell and lateral habenula regulate the development and maintenance of the pain-resilient phenotype, respectively. Together, we establish an approach to explore individual variations in pain response and identify ventral tegmental area glutamatergic neurons and related downstream circuits as critical targets for resilience to socially transferred allodynia and the development of conceptually innovative analgesics.

Original languageEnglish
Article number4947
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

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