To investigate the involvement of the opioid system in curcumin-induced analgesia, the non-selective opioid receptor antagonist naloxone, δ-opioid receptor (DOR) selective antagonist NTI, μ-opioid receptor (MOR) selective antagonist β-FNA, and κ-opioid receptor (KOR) selective antagonist nor-BNI were administered on Day 11 after surgery to bone cancer-bearing mice treated twice daily with curcumin (120 mg/kg, i.p.). This evidence concerns the gene OPRK1 and bone neoplasm.