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The gamma isoforms of protein kinase C (PKC) and the phosphorylation of gamma/epsilon PKC isoforms are increased in the brain in an OIPN model, and PKC inhibitors (Calphostin C, hypericin) attenuate OHP-induced mechanical hyperalgesia [97]

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Subsequently, GSH is synthesized under the catalysis of glutamate cysteine ligase (GCL) and glutathione synthetase (GSS), and finally, GPX4 dependent on GSH converts PLOOH into non-toxic lipophilic alcohols [38]

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Introduction Opioids alter DNA and histone methylation patterns, and gene expression, which contributes to their physiological action and the underlying addictive nature of these drugs (Trivedi et al., 2014a