Abstract
The present study aimed to investigate the effects of high-mobility group box-1 (HMGB-1) on mechanical pain hypersensitivity and the underlying mechanism. Mouse primary astrocytes were isolated and treated as specified. A CCK-8 assay was used to determine cytotoxicity and a gap junctional communication assay was performed. Ethidium bromide (EtBr) uptake was used to evaluate the hemichannel activity of primary astrocytes. A mouse model of neuropathic pain was developed and paw withdrawal threshold was used to evaluate hind paw sensitivity. RT-qPCR and Western blot were used to determine mRNA and protein expression of genes, respectively. ELISA was used to measure the release of inflammatory cytokines. Treatment with HMGB-1 increased the expression of both toll-like receptor-4 (TLR-4) and connexin 43 (Cx43) in mouse primary astrocytes. HMGB-1 also promoted gap junctional intercellular communication and hemichannel function. Our results also demonstrated that HMGB-1-regulated Cx43 through the JNK signaling pathway, and Cx43 was involved in HMGB-1-mediated inflammation in astrocytes. In vivo analysis supported the idea that HMGB-1-induced mechanical hypersensitivity was associated with Cx43. We therefore conclude that HMGB-1-induced mechanical pain hypersensitivity occurs through modulating astrocytic Cx43 via the TLR-4/JNK signaling pathway.
Published Version
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