Actions of midazolam on excitatory transmission in dorsal horn neurons of adult rat spinal cord
Actions of midazolam on excitatory transmission in dorsal horn neurons of adult rat spinal cord
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DOI：
10.1097/00000542-200602000-00020
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发表时间：
2006-02-01
期刊：
影响因子：
8.8
通讯作者：
Baba, H
中科院分区：
文献类型：
--
作者：
Kohno, T;Wakai, A;Baba, H
背景：尽管已发现鞘内注射咪达唑仑（一种水溶性咪唑并苯二氮卓衍生物）可产生镇痛作用，但其如何在脊髓神经元水平发挥这种作用尚不完全清楚。方法：使用全细胞膜片钳技术在成年大鼠脊髓切片的H层神经元中检查咪达唑仑对电诱发和自发兴奋性传导的影响。结果：浴应用咪达唑仑（1μm） A δ 纤维和 C 纤维在振幅和积分区域中诱发多突触兴奋性突触后电流的减弱。然而，它既不影响 A δ 纤维和 C 纤维诱发的单突触兴奋性突触后电流的幅度，也不影响微型兴奋性突触后电流的幅度、频率和衰减时间常数。在苯二氮卓受体拮抗剂氟马西尼（5μm）、咪达唑仑（1μm）存在的情况下，并没有减弱Aδ纤维诱发的多突触兴奋性突触后电流，表明咪达唑仑调节背角的γ-氨基丁酸中间神经元。结论：咪达唑仑通过作用于γ-氨基丁酸型来减少兴奋性突触传递中间神经元中的 A/苯二氮卓受体，导致脊髓背角神经元的兴奋性降低。这可能是咪达唑仑在脊髓中抗伤害的可能机制。
Background: Although intrathecal administration of midazolam, a water-soluble imidazobenzodiazepine derivative, has been found to produce analgesia, how it exerts this effect at the neuronal level in the spinal cord is not fully understood.Methods: The effects of midazolam on electrically evoked and spontaneous excitatory transmission were examined in lamina H neurons of adult rat spinal cord slices using the whole cell patch clamp technique.Results: Bath-applied midazolam (1 mu m) diminished A delta- and C-fiber evoked polysynaptic excitatory postsynaptic currents in both amplitude and integrated area. However, it affected neither A delta- and C-fiber evoked monosynaptic excitatory postsynaptic currents in amplitude nor miniature excitatory postsynaptic currents in amplitude, frequency, and decay time constant. In the presence of a benzodiazepine receptor antagonist, flumazenil (5 mu m), midazolam (1 mu m) did not diminish A delta-fiber evoked polysynaptic excitatory postsynaptic currents, suggesting that midazolam modulate the gamma-aminobutyric acid interneurons in the dorsal horn.Conclusions: Midazolam reduced excitatory synaptic transmission by acting on the gamma-aminobutyric acid type A/benzodiazepine receptor in interneurons, leading to a decrease in the excitability of spinal dorsal horn neurons. This may be a possible mechanism for the antinociception by midazolam in the spinal cord.