Changes in AMPA receptor phosphorylation in the rostral ventromedial medulla after inflammatory hyperalgesia in rats.
To study the glutamatergic mechanisms underlying changes in excitability in the brain stem pain modulatory circuitry after injury, we examined GluR1 serine 831 phosphorylation in the rostral ventromedial medulla (RVM) after complete Freund's adjuvant-induced hindpaw inflammation. Western blots indicated a rapid and prolonged (30 min and 7 days post-inflammation) increase in phosphoserine 831 GluR1 protein levels in the RVM. The upregulated GluR1 phosphorylation was blocked by pretreatment, but not by post-treatment, with the local anesthetic, lidocaine, at the site of inflammation. The upregulation of phosphoserine 831 GluR1 was attenuated by pretreatment with chelerythrine, a selective PKC inhibitor, KN-93, a selective CaMKII inhibitor, and two NMDA receptor antagonists, MK-801 and APV. These findings provide new evidence linking in vivo AMPA receptor phosphorylation in the RVM pain modulatory circuitry to the enhanced descending pain modulation after inflammation.
Department of Biomedical Sciences, Dental School and Program in Neuroscience University of Maryland, Rm. 5A12, 666 W. Baltimore Street, Baltimore, MD 21201, USA.
Yun
Y
Guan
Wei
W
Guo
Meredith T
MT
Robbins
Ronald
R
Dubner
Ke
K
Ren
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009473:Neuronal Plasticity; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015854:Up-Regulation
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005620:Freund's Adjuvant; D010768:Phosphoserine; D011493:Protein Kinase C; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate