Single unit extracellular recordings from dorsal horn neurons were performed with glass micropipettes in pen tobarbital-anesthetized rats. A total of 60 wide dynamic range (WDR) neurons were obtained from 34 rats. In normal rats (20/34), spinally administered D-serine (10 nmol), a putative endogenous agonist of glycine site of NMDA receptors, significantly enhanced the C- but not A beta-, and A delta-fiber responses of WDR neurons in the spinal dorsal horn. When I nmol of the glycine site antagonist 7-chlorokynurenic acid (7-CK) was co-administered with 10 nmol D-serine, the facilitation Of D-serine on C-fiber response was completely blocked. 7-CK (1 nmol) alone failed to influence A beta-, A delta-, and C-fiber responses of WDR neurons. In contrast, in carrageenan-injected rats (14/34), 10 nmol D-serine had no effect on C-fiber response, while 1 nmol 7-CK per se markedly depressed C-fiber response of WDR neurons. These findings Suggest that under physiological conditions, glycine sites in the spinal cord were available but became saturated following peripheral inflammation. Thus, increased endogenous D-serine or glycine may be involved in nociceptive transmission by modulating NMDA receptor activities. The glycine site of NMDA receptors may become a target for the prevention of inflammatory pain. (c) 2006 Elsevier Inc. All rights reserved.