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. 2021 Jul 16;28(6):613–627. doi: 10.1177/10738584211030493

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© The Author(s) 2021

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

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Figure 5. — Schematic illustration of opioid receptors on leukocytes’ surface-mediated synaptic pain pathway. Opioid peptides bind opioid receptors, activating G_i proteins. G-βγ subunits activate phospholipase C (PLC), leading to the second inositol 1,4,5-trisphosphate (IP3) messenger production and subsequent IP3 receptor (IP3R) activation in the endoplasmic reticulum (ER). Ca⁺⁺ ions are released from the ER, leading to the extracellular delivery of intracellular Ca⁺⁺-dependent opioid peptides. Thus, opioid receptors on peripheral nerve cell membranes are activated and pain pathways are inhibited.