The present study investigates the role of serine/threonine protein phosphatase 2A (PP2A) in the modulation of the phosphorylation of the NR1 and NR2B subunits of NMDA receptors in the spinal cord of rats following intradermal injection of capsaicin. The effects of a specific inhibitor of PP2A, fostriecin, on the expression of NR1, phospho-NR1, NR2B, and phospho-NR2B subunits of the NMDA receptor in the spinal cord of rats following noxious stimulation were examined. After continually perfusing with ACSF or fostriecin (3 microM) through a previously implanted microdialysis fiber for 30 min, central sensitization was initiated by injection of capsaicin into the plantar surface of the left paw of rats. The spinal cord was removed at different time points (30, 60, 90, 120, 180 min) after intradermal injection of capsaicin. Western blots were performed to examine the expression of NMDA subunits in spinal cord tissue by using specific antibodies. We found that the upregulated phosphorylation of both NR1 and NR2B subunits induced by capsaicin injection was significantly potentiated by the PP2A inhibitor without affecting the NR1 and NR2B protein itself. These results suggest that PP2A may have a regulatory effect on central sensitization induced by noxious stimuli in the periphery by regulating the phosphorylation state of NMDA receptors.