Involvement of serotonergic, noradrenergic and gabaergic systems in the antinociceptive effect of a ketamine-magnesium sulfate combination in acute pain

Ketamine and magnesium can interact in additive, supra-additive and antagonistic manners in analgesia or anesthesia. Ketamine is a non-competitive NMDA receptor antagonist. Magnesium is an endogenous non-competitive NMDA antagonist that causes anion channel blockade in a dose-dependent manner. It has been established that ketamine and magnesium interact synergistically in the tail-immersion test in rats. To determine the role of serotonergic, GABAergic and noradrenergic systems in analgesia induced by the ketamine-magnesium sulfate combination. Experiments were performed on male Wistar albino rats (200-250 g). Antinociception was evaluated by the tail-immersion test. Methysergide (0.5 and 1 mg/kg, sc) administered alone did not affect nociception in rats. Methysergide (0.5 and 1 mg/kg, sc) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulfate (5mg/kg) combination. Bicuculline (0.5 and 1 mg/kg, sc) given alone did not change the threshold to thermal stimuli in rats. Bicuculline (0.5 and 1 mg/kg, sc) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulfate (5 mg/kg) combination. Yohimbine (0.5, 1 and 3 mg/kg, sc) applied alone did not change nociception. Yohimbine at a dose of 0.5 mg/kg did not influence the effect of ketamine (5 mg/kg)-magnesium sulfate (5 mg/kg), while yohimbine at doses of 1 and 3 mg/kg antagonized the antinociceptive effect of this combination. Serotonergic, noradrenergic and GABAergic systems participate, at least in part, in the antinociceptive effect of the ketamine-magnesium sulfate combination in acute pain in rats.