HMGB1 and rheumatoid arthritis: For example, intrathecal administration1 and bladder instillation27 of disulfide, but not all-thiol, HMGB1 causes pain-like behavior, whereas both isoforms cause excitation of DRG neurons2 and mechanical hypersensitivity after intraplantar injection.53 It is still not known, however, which redox form of peripheral HMGB1 is responsible for joint pain in RA.