Abstract
Central post-stroke pain (CPSP) is one of the most under-recognized consequences of cerebral stroke. However, the development of an effective treatment strategy is urgent because at present, effective therapeutic strategies are minimal. High-mobility group box 1 (HMGB1) has become the focus of experimental and clinical cerebral stroke research. HMGB1 and the receptor for advanced glycation end products (RAGE, one of the receptors of HMGB1) have recently been shown to be critical in the modulation of nociceptive transduction following peripheral neuropathy. The aim of this study was to determine the interactions between CPSP and HMGB1/RAGE signaling. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. Neuronal damage was estimated by histological analysis on day 3 after BCAO. BCAO-induced mechanical allodynia was significantly decreased by the intravenous and intrathecal administration of anti-HMGB1 monoclonal antibody. The expression levels of the HMGB1 protein in the spinal cord and the sciatic nerve were significantly increased on day 3 after BCAO, although no effects of BCAO were noted on RAGE protein expression. The BCAO-induced increase of phosphorylation of extracellular signal-regulated kinase (ERK) was canceled by the administration of anti-HMGB1 monoclonal antibody. In addition, BCAO-induced mechanical allodynia was significantly decreased by intrathecal administration of U0126, an inhibitor of ERK. The results showed that BCAO-induced mechanical allodynia can be regulated by the activation of HMGB1/RAGE signaling.