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The dissociative anesthetic ketamine also has antinociceptive effects. The mechanism and the site of action of such effect of ketamine have been, however, elusive and controversial. The present study was conducted to examine the effect of systemically administered ketamine on spinal nociceptive transmission.We investigated and compared the effects of ketamine (0.25-8 mg/kg) on the hamstring flexor reflex in intact, lightly anesthetized rats and spinally transected rats. The opioid receptor antagonist naloxone was used to examine the involvement of opioid receptors in the actions of ketamine. Finally, the effects of ketamine on dorsal horn neuronal activity to electrical stimulation of peripheral nerves were also studied.Ketamine caused similar dose-dependent depression of the hamstring flexor reflex recorded from spinally intact rats and from spinalized rats. Even the highest dose of ketamine failed to influence the monosynaptic reflex. The depressive effect of ketamine on the flexor reflex was not reversed by naloxone. Ketamine i.v. also exerted a relatively selective inhibition of the responses of dorsal horn wide-dynamic-range neurons to C-fiber input of electrical stimulation of the plantar nerve.Our present results support the notion that ketamine can exert a direct antinociceptive effect in rat spinal cord. Moreover, the data indicated that the spinal antinociceptive effect of ketamine does not involve naloxone-sensitive opioidergic mechanisms.