A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain.

Abstract

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.

• Authors: Samantha M South, Tatsuro Kohno, Brian K Kaspar, Deborah Hegarty, Bryce Vissel, Carrie T Drake, Megumi Ohata, Shirzad Jenab, Andreas W Sailer, Shelle Malkmus, Takashi Masuyama, Philip Horner, Johanna Bogulavsky, Fred H Gage, Tony L Yaksh, Clifford J Woolf, Stephen F Heinemann, Charles E Inturrisi
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 23 Issue 12 Pg. 5031-40 (Jun 15 2003) ISSN: 1529-2401 [Electronic] United States
• PMID: 12832526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• NR1 NMDA receptor
• Receptors, AMPA
• Receptors, N-Methyl-D-Aspartate
• Viral Proteins
• Formaldehyde
• N-Methylaspartate
• Cre recombinase
• Integrases

Topics

• Animals
• Binding Sites
• Dependovirus (genetics)
• Excitatory Postsynaptic Potentials (physiology)
• Female
• Formaldehyde
• Genetic Vectors (administration & dosage, genetics)
• Hyperalgesia (chemically induced, complications, physiopathology)
• In Vitro Techniques
• Integrases (administration & dosage, genetics, metabolism)
• Introns
• Lumbosacral Region
• Male
• Mice
• Mice, Mutant Strains
• Motor Activity (genetics)
• N-Methylaspartate (metabolism)
• Pain (chemically induced, complications, physiopathology)
• Pain Measurement
• Patch-Clamp Techniques
• Posterior Horn Cells (cytology, metabolism, physiology)
• Receptors, AMPA (metabolism)
• Receptors, N-Methyl-D-Aspartate (biosynthesis, deficiency, genetics, metabolism)
• Synaptic Transmission (genetics)
• Transduction, Genetic
• Viral Proteins (administration & dosage, genetics, metabolism)