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

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

doi:10.1523/jneurosci.23-12-05031.2003

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

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

Center for Neuroregeneration

Research output: Contribution to journal › Article › peer-review

167 Scopus citations

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.

Original language	English (US)
Pages (from-to)	5031-5040
Number of pages	10
Journal	Journal of Neuroscience
Volume	23
Issue number	12
DOIs	https://doi.org/10.1523/jneurosci.23-12-05031.2003
State	Published - Jun 15 2003

Keywords

Central sensitization
Conditional knock-out
Cre-loxP
Formalin pain
NMDA receptor
Spinal cord dorsal horn
Synaptic transmission

ASJC Scopus subject areas

Neuroscience(all)

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10.1523/jneurosci.23-12-05031.2003

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South, S. M., Kohno, T., Kaspar, B. K., Hegarty, D., Vissel, B., Drake, C. T., Ohata, M., Jenab, S., Sailer, A. W., Malkmus, S., Masuyama, T., Horner, P., Bogulavsky, J., Gage, F. H., Yaksh, T. L., Woolf, C. J., Heinemann, S. F., & Inturrisi, C. E. (2003). A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain. Journal of Neuroscience, 23(12), 5031-5040. https://doi.org/10.1523/jneurosci.23-12-05031.2003

South, SM, Kohno, T, Kaspar, BK, Hegarty, D, Vissel, B, Drake, CT, Ohata, M, Jenab, S, Sailer, AW, Malkmus, S, Masuyama, T, Horner, P, Bogulavsky, J, Gage, FH, Yaksh, TL, Woolf, CJ, Heinemann, SF & Inturrisi, CE 2003, 'A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain', Journal of Neuroscience, vol. 23, no. 12, pp. 5031-5040. https://doi.org/10.1523/jneurosci.23-12-05031.2003

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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.",

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AU - Hegarty, Deborah

AU - Vissel, Bryce

AU - Drake, Carrie T.

AU - Ohata, Megumi

AU - Jenab, Shirzad

AU - Sailer, Andreas W.

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AU - Masuyama, Takashi

AU - Horner, Philip

AU - Bogulavsky, Johanna

AU - Gage, Fred H.

AU - Yaksh, Tony L.

AU - Woolf, Clifford J.

AU - Heinemann, Stephen F.

AU - Inturrisi, Charles E.

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N2 - 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.

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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

Keywords

ASJC Scopus subject areas

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