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. 2019 Nov 18;13:1218. doi: 10.3389/fnins.2019.01218

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Copyright © 2019 Zortea, Ramalho, Alves, Alves, Braulio, Torres, Fregni and Caumo.

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 representation of neuronal mechanisms underlying opioid tolerance development. Tolerance event: Decreases membrane potential threshold, increases the action-potential duration (APD), and increases neurotransmitter release. APD, action-potential duration; IEG, immediate early genes (c-Fos, FosB); PKA, protein Kinase A; CREB, cAMP response element-binding protein; pCREB, phosphorylated CREB protein; Gi/o, inhibitory G protein; Gs, excitatory G protein; CaMK-II, calcium/calmodulin dependent protein kinase II; PLA2, phospholipase A2; NO, nitric oxide; nNOS, neuronal nitric oxide synthase; HPETE, hydroperoxyeicosatetraenoic acid; +, excitatory; –, inhibitory.