Xiao Chun, Zhang Lin, Cheng Qiu-Ping, Zhang Li-Cai
Research Institute of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, 99 Huaihai West Road, Xuzhou 221002, PR China.
Brain Res. 2008 Jun 18;1215:76-86. doi: 10.1016/j.brainres.2008.03.065. Epub 2008 Apr 6.
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.
背根神经节（DRG）和脊髓背角中的丝裂原活化蛋白激酶（MAPK）激活通过转录依赖性和非依赖性方式导致炎性疼痛。在本研究中，我们调查了大鼠脊髓和DRG中由外周炎症引起的细胞外信号调节蛋白激酶5（ERK5）激活，以及这种激活是否导致热和机械性痛觉过敏反应。将完全弗氏佐剂（CFA）注射到后爪会产生持续性炎症，并使DRG和脊髓背角中的ERK5持续激活。用反义寡核苷酸敲低ERK5可抑制热和机械性痛觉过敏。此外，ERK5的反义敲低降低了CFA诱导的cAMP反应元件结合蛋白（CREB）的磷酸化，CREB是ERK5途径的下游底物，同时也降低了Fos的表达，Fos是中枢神经系统中神经元激活的标志物。我们的研究表明，ERK5信号通路的激活导致外周炎症引起的持续性痛觉过敏。
