To evaluate the direct analgesic effect of ketamine on the spinal cord, rats with chronically implanted catheters in their spinal subarachnoid space were injected intrathecally with the drug. At doses which did not cause gross motor block, ketamine (135–405 μg) produced a small but statistically significant increase in the tail flick latency. Intrathecal pretreatment with saline, naloxone or phentolamine had no effect on the antinociceptive effects of intrathecal ketamine. In contrast, intrathecal methysergide had no effect on the control tail flick latency, but produced a total reversal of the elevated threshold associated with intrathecal ketamine. This suggests involvement of the spinal serotonergic system in the weak antinociceptive effect of intrathecally administered ketamine in the rat. However, even at these doses used a mild local anesthetic effect cannot be ruled out.
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