The involvement of spinal glial cell-derived lipocalin2 in the development of central post-stroke pain

Abstract

Central post-stroke pain (CPSP) is a type of central neuropathic pain, and its mechanisms remain unknown. Recently, we identified a significant increase of lipocalin 2 (LCN2) in the spinal cord of bilateral carotid artery occlusion (BCAO)-induced CPSP model mice using DNA microarray analysis. Generally, LCN2 is synthesized and secreted from activated glial cells. Also, glial cells derived LCN2 play a crucial role in the pathogenesis of neuropathic pain and stroke. In this study, we evaluated whether spinal glial cell-derived LCN2 is involved in the development of central post-stroke pain. Male ddY mice were subjected to 30 min of BCAO. Mechanical hypersensitivity was assessed by the von Frey test. LCN2 protein and its mRNA were evaluated by immunofluorescence stain and real-time PCR, respectively. We tested the expression of LCN2 in lipopolysaccharide (LPS)-activated MG6 microglial cells. BCAO mice showed hypersensitivity against mechanical stimuli and the activation of microglia and astrocyte in the spinal cord 3 days after BCAO. Spinal LCN2 protein was significantly increased and observed in the superficial dorsal horn of BCAO mice. LPS-activated microglial cells significantly and dose-dependently increased LCN2 mRNA expression. These results indicate that LCN2 in the spinal glial cells may involve in the development of CPSP.