Minocycline attenuates the development of neuropathic pain after spinal cord injury by inhibiting the Notch signaling pathway in the dorsolateral prefrontal cortex in mice

Abstract

Previous studies on spinal cord injury (SCI) have mainly focused on the injury site, but the central nervous system (CNS) is a unified whole. SCI can lead to cerebral cortex atrophy, neuronal apoptosis in the brain, an inflammatory response and other pathophysiological changes, which may be important factors affecting the functional recovery and prognosis of patients. A large number of studies have confirmed that after SCI, there are significant changes in microglia and Notch signaling pathways at the injury site, but there have been fewer studies on the changes in the brain. In this study, we observed changes in microglia and the Notch signaling pathway in the dorsolateral prefrontal cortex (dlPFC) in a mouse model of SCI, and the effect of minocycline on these changes was also observed. The results showed that minocycline inhibited the activity of microglia and theNotch signaling pathway. The combination of minocycline and DAPT further inhibited the activity of microglia and Notch signaling pathway, and alleviated neuropathic pain, as indicated by anincrease in the paw withdrawal threshold (PWT) and prolongation of the paw withdrawal latency (PWL). Our results suggested that there are significant changes in the brain after SCI and that these changes in the dlPFC may be related to the occurrence and development of neuropathic pain.