The activation of extracellular signal-regulated protein kinase 5 in spinal cord and dorsal root ganglia contributes to inflammatory pain.
Activation of mitogen-activated protein kinases (MAPKs) in dorsal root ganglia (DRG) and the spinal dorsal horn contributes to inflammatory pain by transcription-dependent and -independent means. In this study, we investigated extracellular signal-regulated protein kinase 5 (ERK5) activation by peripheral inflammation in the spinal cord and DRG of rats and whether this activation contributes to a heat and mechanical hyperalgesia response. Injection of complete Freund's adjuvant (CFA) into a hindpaw produced persistent inflammation and sustained ERK5 activation in DRG and the spinal dorsal horn. Knockdown of the ERK5 by antisense oligonucleotides suppressed the heat and mechanical hyperalgesia. In addition, the antisense knockdown of ERK5 reduced CFA-induced phosphorylation of cAMP response-element binding protein (CREB), a downstream substrate of the ERK5 pathway, and expression of Fos, a marker for neuronal activation in the central nervous system. Our study suggests that activation of the ERK5 signaling pathway contributes to persistent hyperalgesia induced by peripheral inflammation.
Xiao
Chun
C
Research Institute of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, 99 Huaihai West Road, Xuzhou 221002, PR China.
Zhang
Lin
L
Cheng
Qiu-Ping
QP
Zhang
Li-Cai
LC
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000201:enzymology*; D006930:Hyperalgesia / Q000150:complications / Q000201:enzymology; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000201:enzymology*; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010146:Pain / Q000150:complications / Q000201:enzymology*; D020671:Posterior Horn Cells / Q000201:enzymology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D048054:Mitogen-Activated Protein Kinase 7