Presynaptic inhibitory actions of pregabalin on excitatory transmission in superficial dorsal horn of mouse spinal cord: Further characterization of presynaptic mechanisms
Presynaptic inhibitory actions of pregabalin on excitatory transmission in superficial dorsal horn of mouse spinal cord: Further characterization of presynaptic mechanisms
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DOI：
10.1016/j.neulet.2013.11.017
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发表时间：
2014-01-13
影响因子：
2.5
通讯作者：
Hori, Yuuichi
中科院分区：
文献类型：
--
作者：
Matsuzawa, Rie;Fujiwara, Tomonori;Hori, Yuuichi
普瑞巴林广泛用作治疗神经性疼痛的镇痛药。在目前使用小鼠脊髓切片的实验中，我们记录了来自浅表背角神经元的电诱发谷氨酸兴奋性突触后电流（eEPSC）。普瑞巴林降低了 eEPSC 的振幅，并增加了配对脉冲比。普瑞巴林还抑制自发产生的微型 EPSC 的频率，而不影响其幅度。坐骨神经的部分结扎增加了钙通道α2δ-1亚基的表达，并增加了普瑞巴林的突触前抑制作用。鞘内注射针对α2δ-1亚基的反义寡脱氧核苷酸，降低脊髓背角中α2δ-1mRNA的表达，并降低普瑞巴林的作用。这些结果进一步证明普瑞巴林通过以状态依赖性方式与28亚基结合来发挥其突触前抑制作用。此外，普瑞巴林的突触前作用在缺乏突触小泡释放机制的一个组成部分突触融合蛋白 1A 的基因敲除小鼠中减弱，表明突触小泡释放机制的一个组成部分需要突触融合蛋白 1A，普瑞巴林才能充分发挥其突触前抑制作用。这些观察结果可能表明，与构成释放机制的突触前蛋白质的直接和/或间接相互作用是普瑞巴林突触前作用的至少一部分的基础。 (C) 2013 作者。由爱思唯尔爱尔兰有限公司出版。保留所有权利。
Pregabalin is widely used as an analgesic for the treatment of neuropathic pain. In the present experiments using mouse spinal slices, we recorded electrically evoked glutamatergic excitatory postsynaptic currents (eEPSCs) from superficial dorsal horn neurons. Pregabalin reduced the amplitude of eEPSCs, and increased the paired pulse ratio. Pregabalin also inhibited the frequency of spontaneously occurring miniature EPSCs without affecting their amplitude. Partial ligation of the sciatic nerve increased the expression of the calcium channel alpha 2 delta-1 subunit, and increased the presynaptic inhibitory action of pregabalin. Intrathecal injection of antisense oligodeoxynucleotide against the alpha 2 delta-1 subunit, decreased the expression of alpha 2 delta-1 mRNA in the spinal dorsal horn, and decreased pregabalin's action. These results provide further evidence that pregabalin exerts its presynaptic inhibitory action via binding with the 28 subunit in a state-dependent manner. Furthermore, presynaptic actions of pregabalin were attenuated in knockout mice lacking the protein syntaxin 1A, a component of the synaptic vesicle release machinery, indicating that syntaxin 1A is required for pregabalin to exert its full presynaptic inhibitory action. These observations might suggest that direct and/or indirect interactions with the presynaptic proteins composing the release machinery underlie at least some part of pregabalin's presynaptic actions. (C) 2013 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.