Peripheral noxious stimulation induces CREM expression in dorsal horn: involvement of glutamate.
Peripheral noxious stimulation is known to trigger signalling cascades in neurons of the spinal cord. The response to pain and stress at the level of gene expression involves transcriptional activation of several cyclic AMP responsive genes. Here, we show induction of the CREM (cyclic-AMP responsive element modulator) gene in distinct subpopulations of spinal cord neurons upon thermal noxious stimulation. The addition of forskolin or glutamate to cultured spinal cord neurons results in the induction of the CREM isoform, ICER (Inducible cyclic-AMP Early Repressor), a powerful repressor of cAMP-induced transcription. Overexpression of ICER in cultured spinal cord neurons results in the repression of the c-fos and c-jun promoters induced by forskolin and glutamate. On this basis, we postulate that early activation of ICER in spinal cord participates in the attenuation of early gene induction following noxious stimulation.
Naranjo
J R
JR
Instituto Cajal, CSIC, Madrid, Spain.
Mellström
B
B
Carrión
A M
AM
Lucas
J J
JJ
Foulkes
N S
NS
Sassone-Corsi
P
P
D000818:Animals; D002478:Cells, Cultured; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D017781:Genes, Immediate-Early / Q000502:physiology; D016762:Genes, fos / Q000502:physiology; D016758:Genes, jun / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000737:chemistry* / Q000166:cytology*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D018698:Glutamic Acid