Wolff M, Heugel P, Hempelmann G, Scholz A, Mühling J, Olschewski A
Clinic for Anaesthesiology, Intensive Care Medicine, and Pain Therapy, Giessen, Germany.
Br J Anaesth. 2007 Mar;98(3):353-61. doi: 10.1093/bja/ael379.
Clonidine has often been applied in combination with local anaesthetics for spinal or epidural anaesthesia. This study was designed to investigate the local anaesthetic-like action of clonidine in superficial dorsal horn neurones. The superficial laminae of the dorsal horn contain three groups of neurones: tonic-, adapting-, and single-spike-firing neurones which are important neuronal structures for pain transmission, receiving most of their primary sensory input from Adelta and C fibres.
Whole cell patch clamp recordings from spinal cord slices of Wistar rats were used to study the action of clonidine on the generation of single and series of action potentials. Voltage clamp recordings in isolated somata were performed to study the effect of clonidine on voltage-gated Na(+) and different types of K(+) currents.
Firing frequencies of trains of action potentials in tonic-firing neurones are reduced at low concentrations (10 microM) of clonidine, but not in adapting- or single-spike-firing neurones. High concentrations of clonidine (700 microM) are necessary to modify the shape of single action potentials. Low concentrations of clonidine shift the steady-state inactivation curve of Na(+) currents to more negative potentials. At clinical concentrations (6-100 microM) clonidine partially inhibits voltage-gated Na(+) and K(+) channels.
Clonidine suppresses the generation of action potentials in tonic-firing spinal dorsal horn neurones. This may be explained, in part, by an interaction with voltage-gated Na(+) and K(+) currents. Clonidine could therefore contribute to analgesia during local anaesthesia.
可乐定常与局部麻醉药联合用于脊髓或硬膜外麻醉。本研究旨在探讨可乐定在脊髓背角浅层神经元中的局部麻醉样作用。脊髓背角浅层包含三组神经元:紧张性放电神经元、适应性放电神经元和单峰放电神经元,它们是疼痛传递的重要神经结构,主要从Aδ和C纤维接收初级感觉输入。
采用Wistar大鼠脊髓切片的全细胞膜片钳记录技术,研究可乐定对单个动作电位和系列动作电位产生的作用。在分离的胞体上进行电压钳记录,以研究可乐定对电压门控钠通道(Na(+))和不同类型钾通道电流的影响。
低浓度(10μM)可乐定可降低紧张性放电神经元的动作电位发放频率,但对适应性放电或单峰放电神经元无此作用。高浓度(700μM)可乐定才能改变单个动作电位的形状。低浓度可乐定可使Na(+)电流的稳态失活曲线向更负的电位移动。在临床浓度(6 - 100μM)下,可乐定可部分抑制电压门控Na(+)和K(+)通道。
可乐定抑制脊髓背角紧张性放电神经元动作电位的产生。这可能部分是由于其与电压门控Na(+)和K(+)电流相互作用所致。因此,可乐定可能有助于局部麻醉时的镇痛。