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. 2020 May 12;8:269. doi: 10.3389/fcell.2020.00269

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Copyright © 2020 Lin, Qu, Wang, Yang, Hu, Hu, Wu, Jiang, Liu and Han.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Schematic model indicates that glibenclamide alleviates OIH by inhibiting HSP70 release and ER stress. Morphine induces ER stress by the efflux of HSP70. The secretion of HSP70 is under the control of MOR/K_ATP/ERK signal pathway. The efflux of HSP70 leads to the separation of GRP78 from IRE1α, ATF6 and PERK. ER stress enhances PKA-mediated phosphorylation of NMDA receptor which consequently leads to OIH. Glibenclamide as a K_ATP channel blocker inhibits the release of HSP70 induced by morphine, consequently alleviating OIH in rodents.