Baba H, Shimoji K, Yoshimura M
Department of Anesthesiology, Niigata University School of Medicine, Japan.
Anesthesiology. 2000 Feb;92(2):473-84. doi: 10.1097/00000542-200002000-00030.
The activation of descending norepinephrine-containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha2 receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa.
Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated.
In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 microM) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected. This augmentation was mimicked by an alpha1-receptor agonist, phenylephrine (10-60 microM), and inhibited by alpha1-receptor antagonists prazosin (0.5 microM) and 2-(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxane (0.5 microM). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine.
These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha1 receptors, thus providing a mechanism underlying the clinical use of alpha1 agonists with local anesthetics in spinal anesthesia.
源自脑干的下行去甲肾上腺素能纤维的激活可抑制脊髓水平的伤害性感受传递。这些下行去甲肾上腺素能通路如何发挥镇痛作用尚未完全明确。通过α2受体激活导致的脊髓背角（Rexed II层）神经元膜超极化可能是疼痛传递受抑制的原因。此外，去甲肾上腺素可能影响脊髓背角的神经递质释放。
本研究使用成年雄性Sprague-Dawley大鼠（9 - 10周龄，250 - 300 g）。从分离的腰段脊髓切取横向脊髓切片。采用盲法全细胞膜片钳技术记录神经元活动。评估去甲肾上腺素对微小兴奋性和抑制性突触后电流频率及幅度的影响。
在大多数被检测的脊髓背角神经元中，去甲肾上腺素（10 - 100 μM）剂量依赖性增加γ-氨基丁酸（GABA）能和甘氨酸能微小抑制性突触后电流的频率；微小兴奋性突触后电流未受影响。α1受体激动剂苯肾上腺素（10 - 60 μM）可模拟这种增强作用，而α1受体拮抗剂哌唑嗪（0.5 μM）和2-(2,6 - 二甲氧基苯氧基乙基)氨基甲基 - 1,4 - 苯并二恶烷（0.5 μM）可抑制这种增强作用。去甲肾上腺素既不影响对外源性应用的GABA和甘氨酸的突触后反应性，也不影响GABA能和甘氨酸能抑制性突触后电流的动力学。
这些结果表明，去甲肾上腺素通过激活突触前α1受体增强脊髓背角的抑制性突触传递，从而为α1激动剂与局部麻醉药在脊髓麻醉中的临床应用提供了一种机制。
