Research ReportThe 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.