• Ming Jiang, Yulin Huang, Lijun Hu, Hao Wu, Yue Liu, Kun Ni, Xiaokun Zhang, Yu'e Sun, and Xiaoping Gu.
• Department of Anesthesiology, 66506Affiliated Drum Tower Hospital of Nanjing University Medical School, China.
• Mol Pain. 2022 Apr 1; 18: 17448069221099360.

AbstractProlongation of postsurgical pain caused by pre-operative stress is a clinically significant problem, although the mechanisms are not fully understood. Stress can promote the pro-inflammatory activation of microglia, and the transcription factor CCAAT/enhancer-binding protein (C/EBP) β regulates pro-inflammatory gene expression in microglia. Therefore, we speculated that C/EBPβ in spinal microglia may have critical roles in the development of chronic postsurgical pain. Accordingly, in this study, we used a single prolonged stress (SPS) procedure and plantar incisions to evaluate the roles of C/EBPβ in postsurgical pain. Our experiments showed that SPS exposure prolonged mechanical allodynia, increased the expression of C/EBPβ and pro-inflammatory cytokines, and potentiated the activation of spinal microglia. Subsequently, microinjection of C/EBPβ siRNA attenuated the duration of SPS-prolonged postoperative mechanical allodynia and inhibited microglial activation in the spinal cord. Conversely, mimicking this increase in C/EBPβ promoted microglial activation via pretreatment with a pre-injection of AAV5-C/EBPβ, leading to prolongation of postsurgical pain. Overall, these results suggested that spinal microglia may play key roles in prolongation of postsurgical pain induced by pre-operative stress and that C/EBPβ may be a potential target for disease treatment.

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