Iida Ryoji, Iwasaki Ken-ichi, Kato Jitsu, Saeki Shigeru, Ogawa Setsuro
Department of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan.
Anesth Analg. 2007 Sep;105(3):832-7. doi: 10.1213/01.ane.0000275201.64587.1f.
Although intrathecal midazolam has been reported to produce antinociceptive effects mediated by gamma-aminobutyric acid type A-benzodiazepine receptor complexes in the spinal cord, the effects of systemic midazolam on nociception remain unclear. We performed this study to examine the effects of IV-administered midazolam on somatosympathetic Adelta and C reflex discharges in brain-intact cats and decerebrate cats (with transection at midbrain level).
Somatosympathetic Adelta and C reflexes were elicited in the inferior cardiac sympathetic nerve by electrical stimulation of myelinated (Adelta) and unmyelinated (C) afferent fibers of the superficial peroneal nerve in 28 mature cats. After control somatosympathetic reflex responses were obtained, midazolam was administered IV to four groups of randomly allocated cats as follows: brain-intact cats at a dose of 0.03 mg/kg, brain-intact cats at a dose of 0.1 mg/kg, brain-intact cats at a dose of 0.5 mg/kg, and decerebrate cats at a dose of 0.1 mg/kg.
C reflex discharges were significantly augmented at the dose of 0.03 mg/kg and significantly depressed at the dose of 0.1 and 0.5 mg/kg in brain-intact cats. C reflex discharges were also significantly depressed at the dose of 0.1 mg/kg in decerebrate cats.
We have demonstrated that IV midazolam produces dose-related effects on somatosympathetic reflex discharges. The clinical implication of these findings is that the effect of midazolam on nociception depends on its dosage. It also appears that the infra-midbrain region plays a major role in mediating the depressive effects of midazolam on somatosympathetic C reflex discharges.
尽管已有报道称鞘内注射咪达唑仑可通过脊髓中的γ-氨基丁酸A型-苯二氮䓬受体复合物产生抗伤害感受作用,但全身应用咪达唑仑对伤害感受的影响仍不清楚。我们进行了这项研究,以检查静脉注射咪达唑仑对清醒猫和去大脑猫(中脑水平横断)的躯体交感Aδ和C反射放电的影响。
在28只成年猫中,通过电刺激腓浅神经的有髓(Aδ)和无髓(C)传入纤维,在心脏下交感神经中引出躯体交感Aδ和C反射。在获得对照躯体交感反射反应后,将咪达唑仑静脉注射给四组随机分配的猫,如下:清醒猫剂量为0.03mg/kg,清醒猫剂量为0.1mg/kg,清醒猫剂量为0.5mg/kg,去大脑猫剂量为0.1mg/kg。
在清醒猫中,0.03mg/kg剂量时C反射放电显著增强,0.1mg/kg和0.5mg/kg剂量时显著抑制。在去大脑猫中,0.1mg/kg剂量时C反射放电也显著抑制。
我们已经证明静脉注射咪达唑仑对躯体交感反射放电产生剂量相关效应。这些发现的临床意义在于咪达唑仑对伤害感受的影响取决于其剂量。似乎中脑以下区域在介导咪达唑仑对躯体交感C反射放电的抑制作用中起主要作用。