Frequency-dependent ERK phosphorylation in spinal neurons by electric stimulation of the sciatic nerve and the role in electrophysiological activity.

Frequency-dependent ERK phosphorylation in spinal neurons by electric stimulation of the sciatic nerve and the role in electrophysiological activity.
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DOI:
10.1186/1744-8069-3-18
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发表时间:
2007-07-16
期刊:
影响因子:
3.3
通讯作者:
Noguchi K
Noguchi K
中科院分区:
医学3区
文献类型:
--
作者:
Fukui T;Dai Y;Iwata K;Kamo H;Yamanaka H;Obata K;Kobayashi K;Wang S;Cui X;Yoshiya S;Noguchi K

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DRG 和背角神经元中细胞外信号调节激酶 (pERK) 的磷酸化是由 C 纤维电刺激周围神经诱导的。本研究旨在研究重复电刺激产生的大鼠背角神经元中pERK的表达和调节,及其与背角神经元电生理活动的关系。对坐骨神经施加不同频率的C纤维强度的电刺激;分别通过免疫组织化学和细胞外记录研究刺激诱导的背角神经元的 pERK 表达和活性。 C纤维的电刺激(3 mA)以频率依赖性方式诱导背角神经元中的pERK表达,表明电刺激的频率是激活脊髓细胞内信号通路的重要因素。为了证明这种频率依赖性 pERK 表达的潜在机制,在刺激前鞘内给予 NMDA 受体拮抗剂 MK-801 和电压敏感钙通道拮抗剂硝苯地平。我们发现高频(0.5 Hz 和 10 Hz)而非低频(0.05 Hz)刺激诱发的 pERK 被 MK-801 部分抑制。高频和低频刺激诱发的 pERK 均受到硝苯地平治疗的抑制。从 L4-5 背角的 I-II 层和 V 层记录了细胞外单单位活动,我们发现细胞内 ERK 信号的阻断以剂量依赖性方式抑制了结束反应。相反,在施用 ERK 抑制剂后没有观察到机械诱发反应的任何变化。这些观察结果表明 ERK 激活在诱导背角伤害性神经元的结束反应中发挥重要作用。
The phosphorylation of extracellular signal-regulated kinase (pERK) in DRG and dorsal horn neurons is induced by the C-fiber electrical stimulation to the peripheral nerve. The present study was designed to investigate the expression and modulation of pERK in the rat dorsal horn neurons produced by repetitive electrical stimulation, and its involvement in the electrophysiological activity of dorsal horn neurons. Electrical stimulation of C-fiber intensity at different frequencies was applied to the sciatic nerve; the stimuli-induced pERK expression and the activity in dorsal horn neurons were studied by immunohistochemistry and extracellular recording, respectively. Electrical stimulation of C-fibers (3 mA) induced pERK expression in dorsal horn neurons in a frequency-dependent manner, indicating that the frequency of electrical stimulation is an important factor which activates the intracellular signal pathway in the spinal cord. To demonstrate the underlying mechanism of this frequency-dependent pERK expression, an NMDA receptor antagonist, MK-801, and a voltage sensitive calcium channel antagonist, nifedipine, were administrated intrathecally before the stimulation. We found that high frequency (0.5 Hz and 10 Hz) but not low frequent (0.05 Hz) stimulus-evoked pERK was partially inhibited by MK-801. Both high and low frequency stimulus-evoked pERK were inhibited by the nifedipine treatment. The extracellular single unit activities were recorded from the laminae I-II and V of the L4-5 dorsal horn, and we found that blockage of the intracellular ERK signal suppressed the wind-up responses in a dose-dependent manner. In contrast, any change in the mechanically evoked responses was not observed following the administration of ERK inhibitor. These observations indicate that ERK activation plays an important role in the induction of the wind-up responses in dorsal horn nociceptive neurons.
DOI: 10.1038/16040
发表时间: 1999-12-01
影响因子: 25
作者:
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通讯作者: Woolf, CJ
DOI: 10.1074/jbc.m111717200
发表时间: 2002-04-19
影响因子: 4.8
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发表时间: 2005-12-05
期刊: PAIN
影响因子: 7.4
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DOI: 10.1016/j.pain.2004.06.009
发表时间: 2004-09-01
期刊: PAIN
影响因子: 7.4
作者:
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通讯作者: Gereau, RW
DOI: 10.1016/s0896-6273(00)80330-x
发表时间: 1997-06-01
期刊: NEURON
影响因子: 16.2
作者:
Martin, KC;Michael, D;Kandel, ER
通讯作者: Kandel, ER