NR2B receptor blockade inhibits pain-related sensitization of amygdala neurons.
Pain-related sensitization and synaptic plasticity in the central nucleus of the amygdala (CeA) depend on the endogenous activation of NMDA receptors and phosphorylation of the NR1 subunit through a PKA-dependent mechanism. Functional NMDA receptors are heteromeric assemblies of NR1 with NR2A-D or NR3A, B subunits. NMDA receptors composed of NR1 and NR2B subunits have been implicated in neuroplasticity and are present in the CeA. Here we used a selective NR2B antagonist (Ro-256981) to determine the contribution of NR2B-containing NMDA receptors to pain-related sensitization of CeA neurons. Extracellular single-unit recordings were made from CeA neurons in anesthetized adult male rats before and during the development of an acute arthritis. Arthritis was induced in one knee joint by intraarticular injections of kaolin and carrageenan. Brief (15 s) mechanical stimuli of innocuous (100-500 g/30 mm2) and noxious (1000-2000 g/30 mm2) intensity were applied to the knee and other parts of the body. In agreement with our previous studies, all CeA neurons developed increased background and evoked activity after arthritis induction. Ro-256981 (1, 10 and 100 muM; 15 min each) was administered into the CeA by microdialysis 5-6 h postinduction of arthritis. Ro-256981 concentration-dependently decreased evoked responses, but not background activity. This pattern of effect is different from that of an NMDA receptor antagonist (AP5) in our previous studies. AP5 (100 microM - 5 mM) inhibited background activity and evoked responses. The differential effects of AP5 and Ro-256981 may suggest that NMDA receptors containing the NR2B subunit are important but not sole contributors to pain-related changes of CeA neurons.
Ji
Guangchen
G
Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA. guji@utmb.edu
Horváth
Csilla
C
Neugebauer
Volker
V
D000679:Amygdala / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D001168:Arthritis / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010146:Pain / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D013844:Thiazoles