Pre-versus post-formalin effects of intrathecal ketamine on spinal Fos-like immunoreactivity in rats

The spinal expression of the c-Fos immediate early gene in response to formalin pain of the hind paw of rat was used as a marker of neuronal activity. Ketamine, a Nmethyl-D-aspartate (NMDA) receptor antagonist produces analgesic action due to the blockade of glutamate action at the NMDA receptor. Earlier study showed that ketamine acts differently depending on its route of administration. We undertook this study to compare a preemptive suppression of noxious stimulation induced spinal Fos-like immunoreactivity (FLI) after receiving intrathecal ketamine before or after formalin pain.

Male Sprague-Dawley rats received ketamine 1 mg/kg or saline (control group) intrathecally either 5 min before (pre-treatment group) formalin or 5 min after (post-treatment group) formalin (5%, 50 microl) injection. Animals were killed 2 h after the formalin injection, and the lumbar spinal cord was dissected, and processed by immunoperoxidase staining using an antibody against Fos protein.

The FLI was significantly reduced in the pre-treatment group, only laminae I-II of the side ipsilateral to the formalin injection (P < 0.05 vs. control). In laminae V-VI, neither of the ketamine treatment groups showed a significant decrease than the control group.

The results provide evidence that intrathecal ketamine does not have a preemptive blocking effect of FLI expression in whole spinal laminae area. FLI expression of laminae I-II only might not be a good predictor of the ability of agents to produce preemptive effect. The central patterns of activity generated during central sensitization differ regionally in the spinal dorsal horn.