[Analgesic mechanism of ketamine]

The present study was conducted to investigate the mechanism of antinociceptive action of ketamine in rats. Intraperitoneally administered ketamine showed antinociception in the tail flick (TF) and mechanical paw pressure (MPP) tests in a time- and dose-dependent manner. However, intrathecal ketamine, 50-1,000 micrograms, did not exert any antinociceptive effect in TF and MPP tests. In contrast to the antinociceptive actions of intraperitoneal ketamine in TF test in intact rats, ketamine did not produce any effect in spinally transected rats. Further, pretreatment with an intrathecal serotonin antagonist, methysergide, and an intrathecal alpha 2 adrenergic antagonist, yohimbine, abolished the antinociceptive effects of intraperitoneal ketamine in the TF and the MPP tests. The monoamine levels (noradrenaline, MHPG, 5-HT, 5-HIAA) in the spinal cord, which were measured by high performance liquid chromatography, increased after the intraperitoneal administration of ketamine. We conclude that the antinociceptive effects of ketamine involve an activation of the monoaminergic (noradrenergic and serotonergic) descending inhibitory system, and that spinal ketamine does not affect the responses to the acute noxious stimuli.