Although the exact mechanisms by which circadian hormone melatonin attenuates certain adverse effects of chronic opioid use are still unknown, a reduction in pro‐inflammatory and pain‐associated receptor genes, upregulation of the Kcnip3 gene (potassium voltage‐gated channel interacting protein 3; Kcnip3 which plays a role in the regulation of pain sensitivity and anxiety‐ and depression‐like behaviors103), and enhanced levels of antioxidative enzymes have been proposed.100. This evidence concerns the gene KCNIP3 and depressive symptom measurement.