Reactive oxygen species derived from NOX1/NADPH oxidase enhance inflammatory pain
Reactive oxygen species derived from NOX1/NADPH oxidase enhance inflammatory pain
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DOI：
10.1523/jneurosci.1857-08.2008
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发表时间：
2008-09-17
影响因子：
5.3
通讯作者：
Yabe-Nishimura, Chihiro
中科院分区：
文献类型：
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作者：
Ibi, Masakazu;Matsuno, Kuniharu;Yabe-Nishimura, Chihiro
活性氧（ROS）参与炎症过程中对疼痛刺激的敏感性增强（痛觉过敏），但ROS如何以及在何处影响疼痛信号仍然未知。在这里，我们报告了一个新的作用，超氧化物产生NADPH氧化酶的发展痛觉过敏。在小鼠缺乏Nox 1（Nox 1（-/Y）），NADPH氧化酶的催化亚基，热和机械痛觉过敏显着减弱，而没有变化的伤害性反应，热或机械刺激观察。在Nox 1（+/Y）的背根神经节（DRG）神经元中，化学介质缓激肽、5-羟色胺或佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）预处理增强辣椒素诱导的钙升高，而在Nox 1（-/Y）的DRG神经元中，这种升高显著减弱。与此同时，PMA诱导的PKC β转位在ROS清除剂处理的Nox 1（-/Y）或Nox 1（+/Y）DRG神经元中明显受到干扰。在用标记的PKC β转染的细胞中，过氧化氢诱导易位和全长PKC β的游离巯基减少，但不诱导缺乏C1 A结构域的缺失突变体的游离巯基减少。这些结果表明，NOX 1/NADPH氧化酶加速了DRG神经元中PKC β的移位，从而增强了TRPV 1的活性和对疼痛刺激的敏感性。
The involvement of reactive oxygen species (ROS) in an augmented sensitivity to painful stimuli (hyperalgesia) during inflammation has been suggested, yet how and where ROS affect the pain signaling remain unknown. Here we report a novel role for the superoxide-generating NADPH oxidase in the development of hyperalgesia. In mice lacking Nox1 (Nox1(-/Y)), a catalytic subunit of NADPH oxidase, thermal and mechanical hyperalgesia was significantly attenuated, whereas no change in nociceptive responses to heat or mechanical stimuli was observed. In dorsal root ganglia (DRG) neurons of Nox1(+/Y), pretreatment with chemical mediators bradykinin, serotonin, or phorbol 12-myristate 13-acetate (PMA) augmented the capsaicin-induced calcium increase, whereas this increase was significantly attenuated in DRG neurons of Nox1(-/Y). Concomitantly, PMA-induced translocation of PKC epsilon was markedly perturbed in Nox1(-/Y) or Nox1(+/Y) DRG neurons treated with ROS-scavenging agents. In cells transfected with tagged PKC epsilon, hydrogen peroxide induced translocation and a reduction in free sulfhydryls of full-length PKC epsilon but not of the deletion mutant lacking the C1A domain. These findings indicate that NOX1/NADPH oxidase accelerates the translocation of PKC epsilon in DRG neurons, thereby enhancing the TRPV1 activity and the sensitivity to painful stimuli.