High mobility group box-1 (
HMGB1) is associated with the pathogenesis of inflammatory diseases. A previous study reported that
intravenous injection of anti-HMGB1
monoclonal antibody significantly attenuated
brain edema in a rat model of
stroke, possibly by attenuating glial activation.
Peripheral nerve injury leads to increased activity of glia in the spinal cord dorsal horn. Thus, it is possible that the anti-HMGB1 antibody could also be efficacious in attenuating
peripheral nerve injury-induced
pain. Following partial sciatic nerve
ligation (PSNL), rats were treated with either anti-HMGB1 or control
IgG. Intravenous treatment with anti-HMGB1
monoclonal antibody (2 mg/kg) significantly ameliorated PSNL-induced hind paw tactile
hypersensitivity at 7, 14 and 21 days, but not 3 days, after
ligation, whereas control
IgG had no effect on tactile
hypersensitivity. The expression of
HMGB1 protein in the spinal dorsal horn was significantly increased 7, 14 and 21 days after PSNL; the efficacy of the anti-HMGB1 antibody is likely related to the presence of
HMGB1 protein. Also, the injury-induced translocation of
HMGB1 from the nucleus to the cytosol occurred mainly in dorsal horn neurons and not in astrocytes and microglia, indicating a neuronal source of
HMGB1. Markers of astrocyte (
glial fibrillary acidic protein (GFAP)), microglia (ionized
calcium binding adaptor molecule 1 (Iba1)) and spinal neuron (cFos) activity were greatly increased in the ipsilateral dorsal horn side compared to the
sham-operated side 21 days after PSNL. Anti-HMGB1
monoclonal antibody treatment significantly decreased the injury-induced expression of cFos and Iba1, but not GFAP. The results demonstrate that nerve injury evokes the synthesis and release of
HMGB1 from spinal neurons, facilitating the activity of both microglia and neurons, which in turn leads to symptoms of
neuropathic pain. Thus, the targeting of
HMGB1 could be a useful therapeutic strategy in the treatment of
chronic pain.