Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wolff, M; Czorlich, P; Nagaraj, C; Schnöbel-Ehehalt, R; Li, Y; Kwapiszewska, G; Olschewski, H; Heschl, S; Olschewski, A.
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.
Neurosci Res. 2016; 109(5):16-27
Doi: 10.1016/j.neures.2016.02.006
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Olschewski Andrea
- Co-Autor*innen der Med Uni Graz
- Chandran Nagaraj
- Heschl Stefan
- Kwapiszewska-Marsh Grazyna
- Olschewski Horst
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- 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. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Amines - pharmacology
- Amitriptyline - pharmacology
- Analgesics - pharmacology
- Animals -
- Carbamazepine - pharmacology
- Cyclohexanecarboxylic Acids - pharmacology
- Female -
- Gabapentin -
- In Vitro Techniques -
- Male -
- Posterior Horn Cells - drug effects
- Posterior Horn Cells - physiology
- Potassium Channels, Voltage-Gated - metabolism
- Protein Isoforms - metabolism
- Rats -
- Sensory Receptor Cells - drug effects
- Sensory Receptor Cells - physiology
- Voltage-Gated Sodium Channels - metabolism
- gamma-Aminobutyric Acid - pharmacology
- Find related publications in this database (Keywords)
- Lamina I-III
- Spinal cord
- Action potential
- Sensory neurons
- Antidepressants
- Firing pattern