BACKGROUND: N-methyl-D-aspartate (NMDA) antagonists can be useful as preemptive analgesic agents and effective in reducing established central sensitization. The purpose of this study was to evaluate the preemptive effect of intrathecal ketamine and compare the behavioral antinociceptive responses between pre- versus post-formalin ketamine administration in a rat pain model. METHODS: Sprague-Dawley rats (250 - 300 g) were prepared with a PE 10 indwelling intrathecal catheter to receive either saline (control) or ketamine. Rats received ketamine 100ng intrathecally through a catheter either 7 min before or 5 min after formalin. The formalin test was performed with 5% formalin 100nl. The control (n = 8), pre-treatment (n = 7), and post-treatment (n = 7) groups were studied. Pain related behaviors were quantified by counting the incidences of flinching of the formalin injected paw for 60 minutes. RESULTS: Intraplantar formalin injection produced a biphasic (phase 1, 0 - 10 minutes; phase 2, 10 - 60 minutes after formalin injection) response of flinching behavior in control, pre-treatment, and post-treatment groups. The post-treatment group showed less frequent phase 2 flinching than the control group (P < 0.05). CONCLUSIONS: Post-treatment of intrathecal ketamine 100ng was effective on inhibition of phase 2 nociceptive behaviors following the formalin injection. These results suggested that intrathecal ketamine shows an analgesic effect when administered as a post-treatment.