Kohno T, Kumamoto E, Baba H, Ataka T, Okamoto M, Shimoji K, Yoshimura M
Department of Anesthesiology, Niigata University School of Medicine, Japan.
Anesthesiology. 2000 Feb;92(2):507-15. doi: 10.1097/00000542-200002000-00034.
Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord.
The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique.
Bath-applied midazolam (1 microM) prolonged the decay phase of evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); glycine currents were, however, unaltered by midazolam.
Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.
尽管已发现鞘内注射咪达唑仑可产生镇痛作用，但在脊髓的神经元水平上，咪达唑仑如何发挥这种作用尚未完全明确。
采用全细胞膜片钳技术，评估咪达唑仑对成年大鼠脊髓切片胶状质神经元中电诱发或自发抑制性传递以及对外源性γ-氨基丁酸（GABA）、GABA（A）受体激动剂蝇蕈醇或甘氨酸反应产生的影响。
浴加咪达唑仑（1微摩尔）可延长由GABA（A）受体介导的诱发抑制性突触后电流（IPSCs）和微小抑制性突触后电流的衰减期，而幅度不变，同时在衰减期和幅度方面均不影响甘氨酸受体介导的微小抑制性突触后电流。咪达唑仑（0.1微摩尔）可使GABA或蝇蕈醇诱导的电流幅度增加，且这种增加对苯二氮䓬受体拮抗剂氟马西尼（1微摩尔）敏感；然而，甘氨酸电流不受咪达唑仑影响。
咪达唑仑通过作用于胶状质神经元中的GABA（A）-苯二氮䓬受体，增加了GABA介导的突触电流的持续时间以及GABA诱导电流的幅度；这将增强抑制性GABA能传递。这可能是咪达唑仑产生抗伤害感受作用的一种潜在机制。
