Peripheral HMGB1-induced hyperalgesia in mice: Redox state-dependent distinct roles of RAGE and TLR4

Nuclear hmgb1 that contains 3 cysteine residues is acetylated and secreted to the extracellular space,promoting inflammation via multiple molecules such as rage and tlr4. we thus evaluated and characterized the redox state-dependent effects of peripheral hmgb1 on nociception. intraplantar (i.pl.) administration of bovine thymus-derived hmgb1 (bt-hmgb1),all-thiol hmgb1 (at-hmgb1) or disulfide hmgb1 (ds-hmgb1) caused long-lasting mechanical hyperalgesia in mice. the hyperalgesia following i.pl. bt-hmgb1 or at-hmgb1 was attenuated by rage inhibitors,while the ds-hmgb1-induced hyperalgesia was abolished by a tlr4 antagonist. thus,nociceptive processing by peripheral hmgb1 is considered dependent on its redox states. © 2016 japanese pharmacological society. production and hosting by elsevier b.v.