Accumulated evidence implicates the anterior cingulate cortex (ACC) in pain processing. The activation of the NMDA receptor requires the occupation of both the glutamate site and the glycine site. d-Serine released by astrocytes is presumed to be an endogenous ligand for the glycine site of the NMDA receptor. Using whole-cell patch clamp recording, membrane characteristics and effects of exogenous d-serine on NMDA-evoked currents were examined in neurons in ACC slices from normal and complete Freund's adjuvant-induced monoarthritic rats. Neurons from rats with monoarthritis exhibited more depolarized membrane potential, lower firing threshold, lower input resistance and higher slope conductance compared with normal rats. The NMDA-evoked currents were enhanced by d-serine (20 microM) in both normal (135.3+/-4.3% of control, p < 0.01) and arthritic (157.9 +/- 9.7% of control, p < 0.01) rats, respectively. The effect of d-serine was greater in arthritic rats than control rats (p < 0.05). These results suggest that inflammatory pain increased the excitability of ACC neurons, and that the NMDA receptor glycine sites in the ACC neurons were not saturated in either normal or inflammatory pain states.