The Journal of Neuroscience, September 15, 2000, 20(18):6989-6997
Enhanced Phosphorylation of NMDA Receptor 1 Subunits in Spinal
Cord Dorsal Horn and Spinothalamic Tract Neurons after Intradermal
Injection of Capsaicin in Rats
Xiaoju
Zou,
Qing
Lin, and
William D.
Willis
Department of Anatomy and Neuroscience, Marine Biomedical
Institute, The University of Texas Medical Branch, Galveston, Texas
77555-1069
The functional enhancement of NMDA receptors after peripheral
tissue injury is proposed to contribute to the sensitization of
spinothalamic tract (STT) cells and hyperalgesia. Protein
phosphorylation is a major mechanism for the regulation of NMDA
receptor function. In this study, Western blots, immunofluorescence
double labeling, and the retrograde tracing method were used to examine
whether phosphorylation of NMDA receptor 1 (NR1) subunits increases in spinal cord tissue and spinal dorsal horn neurons, especially in STT
cells, after injection of capsaicin (CAP) into the glabrous skin of one
hindpaw of anesthetized rats. Western blots showed that phosphorylated
NR1 protein in spinal cord tissue was increased 30 min after CAP
injection. Immunofluorescence double-labeling staining showed no
significant difference in the number of the NR1-like immunoreactive
neurons in laminae I-VII in the lumbosacral segments
(L4-S1) on the ipsilateral and the
contralateral sides 30 min after CAP or vehicle injection. However, the
numbers of phospho-NR1-like immunoreactive neurons were significantly
increased on the ipsilateral side compared with the vehicle injection
group. STT cells were labeled by bilateral microinjections of the
retrograde tracer fluorogold into the lateral thalamus, including the
ventral-posterior lateral nucleus. Immunofluorescence staining was
performed at 30, 60, and 120 min after CAP injection or at 30 min after
vehicle injection. There was a significant increase in the proportion of STT cells with phosphorylated NR1 subunits compared either with the
contralateral side 30 and 60 min after CAP injection or either side of
animals after intradermal injection of vehicle. These results provide
direct evidence that NMDA receptors in STT cells are phosphorylated
after CAP injection.
Key words:
NMDA receptor subunit; phosphorylation; STT cell; retrograde tracing; dorsal horn; nociception
Copyright © 2000 Society for Neuroscience 0270-6474/00/20186989-09$05.00/0