Journal article

Publication year: 2016

Pages: 16-27

Journal: Neuroscience Research

Volume number: 109

ISSN: 0168-0102

eISSN: 1872-8111

DOI Link: https://doi.org/10.1016/j.neures.2016.02.006

Publisher: Elsevier

Abstract: 
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.

Harvard Citation style: Wolff, M., Czorlich, P., Nagaraj, C., Schnoebel-Ehehalt, R., Li, Y., Kwapiszewska, G., et al. (2016) 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, Neuroscience Research, 109, pp. 16-27. https://doi.org/10.1016/j.neures.2016.02.006

APA Citation style: Wolff, M., Czorlich, P., Nagaraj, C., Schnoebel-Ehehalt, R., Li, Y., Kwapiszewska, G., Olschewski, H., Heschl, S., & Olschewski, A. (2016). 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. Neuroscience Research. 109, 16-27. https://doi.org/10.1016/j.neures.2016.02.006