Evidence of a role for spinal HMGB1 in ischemic stress-induced mechanical allodynia in mice

Brain Research
Wataru MatsuuraShogo Tokuyama

Abstract

We have previously showed that spinal high-mobility group box-1 (HMGB1) plays an important role in the induction of central post-stroke pain (CPSP). It has been reported that HMGB1 exacerbates inflammation and pain via TLR4 or RAGE. Furthermore, the relationship between glial cells, such as microglia and astrocytes, involved in pain exacerbation and HMGB1 has also attracted attention. In this study, we investigated whether the interaction between spinal glial cells and HMGB1 signaling, including its receptors TLR4 or RAGE, is directly involved in the induction of CPSP. Spinal HMGB1 expression increased on day 3 after bilateral carotid artery occlusion (BCAO), and spinal microglia and astrocytes were clearly activated. HMGB1 colocalized with neurons, but not with microglia and astrocytes after BCAO. Intrathecal (i.t.) injection of lipopolysaccharides from Rhodobacter sphaeroides (LPS-RS, a TLR4 antagonist) and low-molecular-weight heparin (LMWH, a RAGE antagonist) significantly blocked mechanical allodynia on day 3 after BCAO. BCAO-induced activation of spinal microglia and astrocyte were suppressed by i.t. anti-HMGB1 monoclonal antibody (mAb) and LPS-RS administration. In addition, i.t. injection of NG-nitro-l-arginine methyl e...Continue Reading

Citations

Aug 2, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Kazutaka ShinozukaCesario V Borlongan
Nov 19, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Atsufumi KawabataRyuichi Tsujita
Jan 6, 2021·International Journal of Molecular Sciences·Fumiko Sekiguchi, Atsufumi Kawabata

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