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.

INVOLVEMENT OF SEROTONERGIC, NORADRENERGIC AND GABAERGIC SYSTEMS IN THE ANTINOCICEPTIVE EFFECT OF A KETAMINE-MAGNESIUM SULFATE COMBINATION IN ACUTE PAIN