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Central post-stroke pain (CPSP) is one of the most under-recognized consequences of cerebral stroke, but the development of an effective treatment strategy is urgent. High-mobility group box 1 (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. 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. BCAO-induced mechanical allodynia was significantly decreased by the intravenous and intrathecal administration of anti-HMGB1 monoclonal antibody. 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. [ABSTRACT FROM AUTHOR]

Activation of vagus nerve exerts orexin-A (OXA)-mediated suppression of post-ischemic glucose intolerance and cerebral ischemic neuronal damage. Cerebral ischemia induces hepatic inflammatory factors and contributes to the development of hepatic insulin resistance by activating sympathetic nerves. However, it is not enough to understand whether OXA regulates these phenomena through activation of vagus nerve. In this study, we demonstrated that the involvement of OXA-induced activation of vagus nerve in the induction of hepatic inflammatory factors by cerebral ischemia. Focal cerebral ischemic model construction was performed by 2 h of middle cerebral artery occlusion (MCAO) in ddY male mice. OXA-positive neurons were visualized using the retrograde tracer Fluoro-Gold™. Intrahypothalamic OXA (5 pmol/mouse) administration significantly suppressed the MCAO-induced post-ischemic glucose intolerance and neuronal damage. The MCAO-induced decrease in hepatic insulin receptors and increase in hepatic gluconeogenic enzymes were suppressed by OXA administration. These effects were canceled by N -butylscopolamine (a muscarinic receptor antagonist). MCAO-induced increases in hepatic F4/80, tumor necrosis factor-α, and interleukin-1β on day 1 after MCAO were reversed by OXA administration. These effects were abolished by N -butylscopolamine or hepatic vagotomy. These results suggest that OXA-induced activation of vagus nerve regulates the post-ischemic elevation of hepatic inflammatory factors, and which may be contributed to part of OXA-mediated regulation of post-ischemic glucose intolerance. [ABSTRACT FROM AUTHOR]