Amitriptyline and carbamazepine utilize voltage-gated ion channel suppression to impair excitability of sensory dorsal horn neurons in thin tissue slice: An in vitro study

被引：12

作者：

Wolff, Matthias ^{[1
]}

Czorlich, Patrick ^{[2
]}

Nagaraj, Chandran ^{[3
]}

Schnoebel-Ehehalt, Rose ^{[1
]}

Li, Yingji ^{[4
]}

Kwapiszewska, Grazyna ^{[3
,5
]}

Olschewski, Horst ^{[4
]}

Heschl, Stefan ^{[5
]}

Olschewski, Andrea ^{[3
,5
]}

机构：

[1] Univ Giessen, Dept Anaesthesiol, Intens Care Med, Pain Therapy, Giessen, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, Hamburg, Germany

[3] Ludwig Boltzmann Inst Lung Vasc Res, Graz, Austria

[4] Med Univ Graz, Dept Internal Med, Div Pulmonol, Graz, Austria

[5] Med Univ Graz, Dept Anaesthesia & Intens Care Med, Graz, Austria

来源：

NEUROSCIENCE RESEARCH | 2016年 / 109卷

关键词：

Lamina I-III; Spinal cord; Action potential; Sensory neurons; Antidepressants; Firing pattern; SUBSTANTIA-GELATINOSA NEURONS; ROOT GANGLION NEURONS; RAT SPINAL-CORD; K+ CHANNELS; NEUROPATHIC PAIN; ALPHA-SUBUNITS; NA+ CHANNELS; CURRENTS; SODIUM; GENERATION;

D O I：

10.1016/j.neures.2016.02.006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Amitriptyline, carbamazepine and gabapentin are often used for the treatment of neuropathic pain. However, their analgesic action on central sensory neurons is still not fully understood. Moreover, the expression pattern of their target ion channels is poorly elucidated in the dorsal horn of the spinal cord. Thus, we performed patch-clamp investigations in visualized neurons of lamina I-III of the spinal cord. The expression of the different voltage-gated ion channels, as the targets of these drugs, was detected by RT-PCR and immunohistochemistry. Neurons of the lamina I-III express the TTX-sensitive voltage gated Na+ as well as voltage-gated K+ subunits assembling the fast inactivating (A-type) currents and the delayed rectifier K+ currents. Our pharmacological studies show that tonically-firing, adapting-firing and single spike neurons responded dose-dependently to amitriptyline and carbamazepine. The ion channel inhibition consecutively reduced the firing rate of tonically-firing and adapting-firing neurons. This study provides evidence for the distribution of voltage-gated Na+ and K+ subunits in lamina I-III of the spinal cord and for the action of drugs used for the treatment of neuropathic pain. Our work confirms that modulation of voltage-gated ion channels in the central nervous system contributes to the antinociceptive effects of these drugs. (C) 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

引用

页码：16 / 27

页数：12