c-Jun N-terminal kinase activation in dorsal root ganglion contributes to pain hypersensitivity
c-Jun N-terminal kinase activation in dorsal root ganglion contributes to pain hypersensitivity
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DOI：
10.1016/j.bbrc.2005.07.055
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发表时间：
2005-09-16
影响因子：
3.1
通讯作者：
Yamashita, T
中科院分区：
文献类型：
--
作者：
Doya, H;Ohtori, S;Yamashita, T
炎症性疼痛的特征是痛觉阈值的降低，是由炎症介质的作用引起的。丝裂原活化蛋白激酶级联参与外周伤害性致敏。我们研究了c-Jun n-末端激酶（JNK）在炎症性痛觉过敏的早期参与背根神经节（DRG）。足底内注射完全弗氏佐剂可在30分钟内诱导DRG神经元JNK的激活。JNK抑制剂SP600125对大鼠进行预处理和后处理后，通过爪脱潜伏期和背角神经元c-fos免疫反应性上调来评估，显著减轻了热痛觉过敏。一个i.pl。注射神经生长因子（NGF）可诱导JNK磷酸化和热痛觉过敏，SP600125可改善痛觉过敏。抑制剂实验表明，JNK和细胞外信号调节蛋白激酶协同作用于初级伤害感觉神经元。这些发现表明JNK是治疗炎症性疼痛超敏反应的治疗靶点。(c) 2005爱思唯尔公司版权所有。
Inflammatory pain, characterized by a decrease in the nociceptive threshold, arises through the actions of inflammatory mediators. Mitogen-activated protein kinase cascades participate in peripheral nociceptive sensitization. We examined the involvement of c-Jun N-terminal kinase (JNK) in the dorsal root ganglion (DRG) in the early phase of inflammation-induced hyperalgesia. An intra-plantar (i.pl.) injection of complete Freund's adjuvant induced the activation of JNK in DRG neurons within 30 min. Pretreatment as well as post-treatment of rats with a JNK inhibitor, SP600125, significantly attenuated thermal hyperalgesia, as assessed by paw-withdrawal latency, and the upregulation of c-fos immunoreactivity in dorsal horn neurons. An i.pl. injection of nerve growth factor (NGF) also induced the phosphorylation of JNK as well as thermal hyperalgesia, and SP600125 improved hyperalgesia. Inhibitor experiments suggest that JNK and extracellular signal-regulated protein kinase act on primary nociceptive neurons synergistically. These findings demonstrate that JNK is a therapeutic target for treating inflammation-induced pain hypersensitivity. (c) 2005 Elsevier Inc. All rights reserved.