A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain.
To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86-88% in lamina II neurons. The spatial NR1 knock-out does not alter heat or cold paw-withdrawal latencies, mechanical threshold, or motor function. However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury.
South
Samantha M
SM
Department of Pharmacology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Kohno
Tatsuro
T
Kaspar
Brian K
BK
Hegarty
Deborah
D
Vissel
Bryce
B
Drake
Carrie T
CT
Ohata
Megumi
M
Jenab
Shirzad
S
Sailer
Andreas W
AW
Malkmus
Shelle
S
Masuyama
Takashi
T
Horner
Philip
P
Bogulavsky
Johanna
J
Gage
Fred H
FH
Yaksh
Tony L
TL
Woolf
Clifford J
CJ
Heinemann
Stephen F
SF
Inturrisi
Charles E
CE
D000818:Animals; D001665:Binding Sites; D000229:Dependovirus / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D005557:Formaldehyde; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006930:Hyperalgesia / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D066298:In Vitro Techniques; D019426:Integrases / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D007438:Introns; D008161:Lumbosacral Region; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics; D016202:N-Methylaspartate / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D010147:Pain Measurement; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics; D014161:Transduction, Genetic; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism
C409466:NR1 NMDA receptor; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014764:Viral Proteins; D005557:Formaldehyde; D016202:N-Methylaspartate; C045073:Cre recombinase; D019426:Integrases