Inflammatory pain-induced signaling events following a conditional deletion of the N-methyl-d-aspartate receptor in spinal cord dorsal horn Journal Article


Authors: Cheng, H. T.; Suzuki, M.; Hegarty, D. M.; Xu, Q.; Weyerbacher, A. R.; South, S. M.; Ohata, M.; Inturrisi, C. E.
Article Title: Inflammatory pain-induced signaling events following a conditional deletion of the N-methyl-d-aspartate receptor in spinal cord dorsal horn
Abstract: The N-methyl-d-aspartate (NMDA) receptor in the spinal cord dorsal horn (SCDH) is one of the mechanisms involved in central sensitization during chronic pain. Previously, this laboratory created a spatio-temporal knockout (KO) of the N-methyl-d-aspartate receptor I (NR1) subunit in the mouse SCDH. The NR1 KO completely blocks NR1 gene and subsequent NMDA receptor expression and function in SCDH neurons. In the NR1 KO mice, the mechanical and cold allodynia induced at 24 h after complete Freund's adjuvant (CFA) was reduced. However, the protective effects of KO were transient and were not seen at 48 h after CFA. These observations suggest the presence of NMDA-independent pathways that contribute to CFA-induced pain. CFA induces the activation of several signaling cascades in the SCDH, including protein kinase C (PKC)γ and extracellular signal-regulated kinases (ERK1/2). The phosphorylation of PKCγ and ERK1/2 was inhibited in the SCDH of NR1 KO mice up to 48 h after CFA treatment, suggesting that these pathways are NMDA receptor-dependent. Interestingly, neuronal cyclooxygenase (COX) -2 expression and microglial p38 phosphorylation were induced in the SCDH of the NR1 KO at 48 h after CFA. Our findings provide evidence that inflammatory reactions are responsible for the recurrence of pain after NR1 KO in the SCDH. © 2008 IBRO.
Keywords: signal transduction; controlled study; protein expression; protein phosphorylation; gene deletion; nonhuman; mouse; animals; mice; animal tissue; pain; green fluorescent protein; animal experiment; animal model; inflammation; enzyme activation; phosphorylation; time factors; viral gene delivery system; mice, transgenic; enzyme phosphorylation; cyclooxygenase 2; spinal cord; mitogen activated protein kinase 1; mitogen activated protein kinase 3; extracellular signal-regulated map kinases; green fluorescent proteins; protein kinase c; n methyl dextro aspartic acid receptor 1; analysis of variance; cre recombinase; hyperalgesia; pain threshold; knockout gene; protein kinase c gamma; synaptophysin; gene expression regulation, enzymologic; allodynia; physical stimulation; cyclooxygenase-2; microglia; freund's adjuvant; inflammatory pain; spinal cord dorsal horn; freund adjuvant; receptors, n-methyl-d-aspartate; n-methyl-d-aspartate receptor; mitogen activated protein kinases; p38; protein kinase cγ; virus recombination; posterior horn cells
Journal Title: NeuroReport
Volume: 155
Issue: 3
ISSN: 0959-4965
Publisher: Lippincott Williams & Wilkins  
Date Published: 2008-08-26
Start Page: 948
End Page: 958
Language: English
DOI: 10.1016/j.neuroscience.2008.06.024
PUBMED: 18621103
PROVIDER: scopus
PMCID: PMC2556960
DOI/URL:
Notes: --- - "Cited By (since 1996): 13" - "Export Date: 17 November 2011" - "CODEN: NRSCD" - "Source: Scopus"
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  1. Hsin Lin T Cheng
    1 Cheng