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.
Consecutive injection of both RAGE antagonist FPS-ZM1 (i.t.) and STAT3 activity inhibitor S3I-201 (i.t.) inhibited the enhanced excitability of DRG neurons and mechanical allodynia induced by NP implantation.
Thus, at-HMGB1 activation through RAGE may be responsible for sensory neuron sensitization and mechanical hyperalgesia associated with chronic neuropathic pain states.