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 Abeta-, and Adelta-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 Abeta-, Adelta-, 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.
Institute of Neurobiology, Fudan University, Shanghai 200433, China.
Ji-Dong
JD
Guo
Hua
H
Wang
Yu-Qui
YQ
Zhang
Zhi-Qi
ZQ
Zhao
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002351:Carrageenan; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007267:Injections; D008297:Male; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012694:Serine / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D002351:Carrageenan