Background: The glycine site of NMDA receptor complex has been involved in the modulation of nociceptive transmission in the spinal cord. The aim of this study was to evaluate the effects of intrathecal glycine site antagonists, 4161 and 4162, on the stimulus evoked by formalin injection or radiant heat, and determine the regulatory role of the glycine site for the noxious stimulation. Methods: Rats were implanted with lumbar intrathecal catheters. 4161 and 4162 were intrathecally administered 10 min before nociceptive tests. After application of formalin injection or radiant heat, nociceptive behaviors (flinching response or latency) were observed for 120 or 60 min, respectively. Results- Intrathecal administration of glycine site antagonists, 4161 and 4162, produced a dose-dependent suppression of flinches in both phases in the formalin test and increased the latency of paw withdrawal in Hot-Box test. Conclusions: Taken together, spinal administration of 4161 and 4162 may be useful in management of acute pain and the facilitated state pain.

Keywordsantinociception, formalin test, glycine site antagonist, hemodynamics, rat, spinal cord.