Different effects of local anesthetics on extracellular signal-regulated kinase phosphorylation in rat dorsal horn neurons.
Different effects of local anesthetics on extracellular signal-regulated kinase phosphorylation in rat dorsal horn neurons.
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DOI：
10.1016/j.ejphar.2014.03.048
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发表时间：
2014-07
影响因子：
5
通讯作者：
Lianxi Zhang;K. Tanabe;F. Yanagidate;Y. Kawasaki;Guihua Chen;S. Dohi;H. Iida
中科院分区：
文献类型：
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作者：
Lianxi Zhang;K. Tanabe;F. Yanagidate;Y. Kawasaki;Guihua Chen;S. Dohi;H. Iida
局部麻醉药是神经元电压门控Na+通道阻滞剂，也影响多种其他离子通道、N-甲基-D-谷氨酸（NMDA）受体和α-氨基-3-羟基-5-甲基-4-咪唑丙酸（AMPA）受体。从突触前纤维释放的谷氨酸通过NMDA和AMPA受体激活脊髓背角神经元的细胞外信号调节激酶（ERK）。ERK在中枢敏感化中起关键作用，这有助于疼痛的慢性化。我们研究了四种代表性的局部麻醉药，利多卡因，丁卡因，左旋布比卡因，罗哌卡因对ERK磷酸化诱导的辣椒素，释放谷氨酸从突触前神经元，NMDA，AMPA，或离子霉素，钙离子载体，在背神经元。我们观察到辣椒素诱导的ERK磷酸化，这是抑制利多卡因，丁卡因，或罗哌卡因，但不是由左旋布比卡因。NMDA诱导的ERK磷酸化被利多卡因、丁卡因或左布比卡因抑制，但不被罗哌卡因抑制。AMPA诱导的ERK磷酸化被利多卡因或丁卡因抑制，但不被左旋布比卡因或罗哌卡因抑制。最后，利多卡因、丁卡因或罗哌卡因可抑制离子霉素诱导的ERK磷酸化，但左旋布比卡因则不能。我们的研究结果表明，局麻药有助于预防不同强度和不同作用机制的持续性术后疼痛的发生。
Local anesthetics, which are widely known to be neuronal voltage-gated Na+channel blockers, also affect a variety of other ion channels,N-methyl-d-asparate (NMDA) receptors and α-amino-3-hydroxy-5-methyl-4-izoxazolepropionic acid (AMPA) receptors. Glutamate, which is released from presynaptic fibers, activates extracellular signal-regulated kinase (ERK) through NMDA and AMPA receptors in spinal dorsal horn neurons. ERK plays a key role in central sensitization, which contributes to the chronicity of pain. We investigated the effects of four representative local anesthetics, lidocaine, tetracaine, levobupivacaine, and ropivacaine on ERK phosphorylation induced by capsaicin, which releases glutamate from presynaptic neurons, NMDA, AMPA, or ionomycin, a calcium ionophore, in dorsal neurons. We observed capsaicin-induced phosphorylation of ERK, which was suppressed by lidocaine, tetracaine, or ropivacaine, but not by levobupivacaine. NMDA-induced phosphorylation of ERK was suppressed by lidocaine, tetracaine, or levobupivacaine, but not by ropivacaine. AMPA-induced phosphorylation of ERK was suppressed by lidocaine or tetracaine, but not by levobupivacaine or ropivacaine. Finally, ionomycin-induced ERK phosphorylation was suppressed by lidocaine, tetracaine, or ropivacaine, but not by levobupivacaine. Our results suggest that local anesthetics contribute to the prevention of the incidence of persistent postsurgical pain with varying intensities and through different mechanisms of action.