Distinct effects of d-serine on spinal nociceptive responses in normal and carrageenan-injected rats

Single unit extracellular recordings from dorsal horn neurons were performed with glass micropipettes in pentobarbital-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 Aβ-, and Aδ-fiber responses of WDR neurons in the spinal dorsal horn. When 1 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 Aβ-, Aδ-, 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.