Background and aims: Ketamine (KT) and magnesium (MG) can interact in an additive, synergistic and antagonistic manner in causing analgesia or anesthesia. Opioid system is involved in the analgesic effect of the combination of KT and MG. Aim of our study was to examine which type of opioid receptors were involved in analgesic effect of the KT-MG combination.
Methods: Antinociception was tested in the rat orofacial formalin test, a model of trigeminal pain. Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. Animals were divided into groups: control, KT + MG, KT + MG + antagonist, antagonist. Antagonist such as naloxone (non-selective opioid antagonist), CTAP (selective mu opioid receptor antagonist) and nor-binaltorphimine (selective kappa-opioid receptor antagonist) were used in experiments.  

Results: Naloxone (3 mg/kg) antagonized analgesic effect of KT-MG combination at all time points phase of the orofacial formalin test. CTAP (1 mg/kg) antagonized combination at all time points. Nor-binaltorphimine (1 mg/kg) in combination with KT-MG showed significant difference in pain relieving compared to combination without antagonist only at  in the second phase of the orofacial formalin test. 

Conclusions: Analgesic effect of combination of  KT and MG is mediated through opioid system especially through  mu opioid receptor but partially through kappa-opioid receptors.

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