期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 20, 期 2, 页码 375-384出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1111/j.1460-9568.2004.03506.x
关键词
dorsal horn; plasticity; rat; spinal cord
资金
- NINDS NIH HHS [K08 NS044139, K08 NS44139, R01 NS040698, R01 NS039518, R01 NS038253] Funding Source: Medline
The N-methyl-D-aspartate receptor (NMDAR) contributes to central sensitization in the spinal cord and the generation of pain hypersensitivity. NMDAR function is modulated by post-translational modifications including phosphorylation, and this is proposed to underlie its involvement in the production of pain hypersensitivity in the spinal cord. We now, show that a noxious heat stimulus applied to the rat hindpaw induces phosphorylation of the NMDAR NR1 subunit at a protein kinase C (PKC)-dependent site, serine-896, in superficial dorsal horn neurons. Phosphorylation of NRII serine-896 is essentially absent in the superficial dorsal horn laminae of naive rats, but, there is rapid (<2 min) induction following a noxious but not in-nocuous heat stimulus. The number of pNR1-immunoreactive neuronal profiles in the superficial dorsal horn peaks 30 min after noxious heat stimulation and persists for up to 1 h. pNR1serine896 induction occurs in the endoplasmic reticulum, suggesting that it contributes to trafficking of the receptor from intracellular stores to the membrane. The phosphorylation of the subunit is attenuated by intrathecal injection of the. NMDAR antagonist, MK801, suggesting that the NMDAR is involved via a feed-forward mechanism in its own phosphorylation. The pNR1serine896-positive neurons are highly co-localized with PKCdelta and only rarely with PKCgamma. These data provide evidence for an activity-dependent NMDAR phosphorylation at the PKC-dependent site, serine-896, in spinal cord dorsal horn neurons initiated by peripheral noxious stimuli.
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