High‐mobility group box‐1 induces mechanical pain hypersensitivity through astrocytic connexin 43 via the toll‐like receptor‐4/JNK signaling pathway. Issue 2 (19th August 2020)

• Record Type: Journal Article
• Authors: Liu, Jiang; Li, Xiuhua; Ke, Ana
• Is Part Of: Synapse. Volume 75:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-19
• Subjects: adipocyte -- HMGB‐1 -- JNK -- mechanical pain hypersensitivity -- TLR‐4; Synapses -- Periodicals; 612
• DOI: 10.1002/syn.22184
• Languages: English
• ISSNs: 0887-4476

Abstract

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. Abstract : The study demonstrated that HMGB‐1 induced mechanical pain hypersensitivity through astrocytic connexin 43 via the TLR‐4/ JNK signaling pathway.