Prolongation 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.