The aim of the present study was to investigate the mechanism by which dexmedetomidine (DEX) alleviates neuropathic pain in a chronic constriction injury (CCI) model in rats. A CCI rat model was established through sciatic nerve ligation. CCI rats were treated with DEX, the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385, the NLR family pyrin domain containing 3 (NLRP3) antagonist MCC950 and/or the NLRP3 activator nigericin. The mechanical withdrawal threshold (MWT) was measured to assess the pain sensitivity of CCI rats. Hematoxylin and eosin staining and TUNEL staining were used to examine spinal injury and apoptosis, respectively. ELISA was used to quantify the levels of inflammatory factors. The expression levels of Nrf2 and NLRP3 were also examined. The results indicated that a decrease in MWT and increases in spinal cord injury, apoptosis and inflammatory factors were detected in CCI rats compared with control rats. Spinal inflammation was abrogated in DEX-treated CCI rats. Compared with the model group, an increase in MWT and decreases in spinal cord injury, apoptosis and inflammatory factors were detected in rats treated with MCC950, while the opposite effects were observed in rats treated with nigericin. The opposite effects on these indicators were observed in the DEX + ML385 and MCC950 + ML385 groups compared with the DEX and MCC950 groups, respectively. MWT was increased, while spinal cord injury, apoptosis and inflammation decreased in the nigericin + DEX group compared with the nigericin group. In summary, the results of the present study indicated that DEX reduced neuropathic pain in CCI rats by suppressing NLRP3 through Nrf2 activation.

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Objective: To investigate the mechanism of dexmedetomidine (DEX) involving Nrf2-dependent inhibition of NLRP3 in relieving neuropathic pain in chronic constriction injury (CCI) rat models.Methods: The CCI rat models were constructed through sciatic nerve ligation. The CCI rats were treated with DEX, Nrf2 inhibitor (ML385), NLRP3 antagonist (MCC950) and NLRP3 activator (Nigericin). Mechanical withdrawal threshold (MWT) was measured to test the pain sensitivity of CCI rats. H&E staining detected spinal injury of the rats and TUNEL staining was applied to test apoptosis in the spinal cords. ELISA measured the expressions of inflammatory factors. The expressions of Nrf2 and NLRP3 were also detected.Results: Decreased MWT, enhanced spinal cord injury, promoted apoptosis and increased inflammatory factors were detected in CCI rats. The expressions of the above indicators were retraced in DEX-treated CCI rats. Increased MWT, reduced spinal cord injury, inhibited apoptosis and decreased inflammatory factors were detected in rats treated with MCC950 or ML385 while opposite expression patterns were found in rats treated with Nigericin. The expressions of these indicators were retraced in both DEX+ML385 group and MCC950+ML385 group compared to ML385 group and MCC950 group respectively.Conclusion: DEX reduces neuropathic pain of CCI rats by suppressing NLRP3 through activation of Nrf2.

The concept of installing energy dissipation devices in a coupling beam of shear wall structures has been proposed and investigated. The energy dissipation device is used to dissipate seismic energy and is easy to be replaced in the post-earthquake event. According to the practical design methods of replaceable coupling beams, some selected conventional coupling beams installed replaceable energy dissipation devices. Two bench-mark models are built in ABAQUS program, one with conventional coupling beams (CBM model) while the other with replaceable coupling beams (NBM model). Modal analysis, response spectrum and earthquake time-history analysis are conducted to verify the advantage of replaceable coupling beams. It was found that the inter-story drift angle and damage of the NBM model was smaller than CBM model. Moreover, the damage of the replaceable coupling beams mainly concentrated in energy dissipation devices, while the other parts of replaceable coupling beams kept intact. In contrast, the conventional coupling beams produced irreversible damage, which is more difficult to restore after earthquake.