Medizinische Universität Graz - Research portal

Logo MUG Resarch Portal

Selected Publication:

Bräu, ME; Dreimann, M; Olschewski, A; Vogel, W; Hempelmann, G.
Effect of drugs used for neuropathic pain management on tetrodotoxin-resistant Na(+) currents in rat sensory neurons.
Web of Science PubMed FullText


Authors Med Uni Graz:
Olschewski Andrea

Dimensions Citations:

Plum Analytics:
BACKGROUND: Tetrodotoxin-resistant Na(+) channels play an important role in generation and conduction of nociceptive discharges in peripheral endings of small-diameter axons of the peripheral nervous system. Pathophysiologically, these channels may produce ectopic discharges in damaged nociceptive fibers, leading to neuropathic pain syndromes. Systemically applied Na(+) channel--blocking drugs can alleviate pain, the mechanism of which is rather unresolved. The authors investigated the effects of some commonly used drugs, i.e., lidocaine, mexiletine, carbamazepine, amitriptyline, memantine, and gabapentin, on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglia. METHODS: Tetrodotoxin-resistant Na(+) currents were recorded in the whole-cell configuration of the patch-clamp method in enzymatically dissociated dorsal root ganglion neurons of adult rats. Half-maximal blocking concentrations were derived from concentration-inhibition curves at different holding potentials (-90, -70, and -60 mV). RESULTS: Lidocaine, mexiletine, and amitriptyline reversibly blocked tetrodotoxin-resistant Na(+) currents in a concentration- and use-dependent manner. Block by carbamazepine and memantine was not use-dependent at 2 Hz. Gabapentin had no effect at concentrations of up to 3 mm. Depolarizing the membrane potential from -90 mV to -60 mV reduced the available Na(+) current only by 23% but increased the sensitivity of the channels to the use-dependent blockers approximately fivefold. The availability curve of the current was shifted by 5.3 mV to the left in 300 microm lidocaine. CONCLUSIONS: Less negative membrane potential and repetitive firing have little effect on tetrodotoxin-resistant Na(+) current amplitude but increase their sensitivity to lidocaine, mexiletine, and amitriptyline so that concentrations after intravenous administration of these drugs can impair channel function. This may explain alleviation from pain by reducing firing frequency in ectopic sites without depressing central nervous or cardiac excitability.
Find related publications in this database (using NLM MeSH Indexing)
Amitriptyline - pharmacology
Analgesics - pharmacology
Anesthetics, Local - pharmacology
Animals - pharmacology
Cells, Cultured - pharmacology
Diethylcarbamazine - pharmacology
Drug Interactions - pharmacology
Electric Stimulation - pharmacology
Lidocaine - pharmacology
Memantine - pharmacology
Membrane Potentials - drug effects
Mexiletine - pharmacology
Neurons, Afferent - drug effects
Patch-Clamp Techniques - drug effects
Rats - drug effects
Rats, Wistar - drug effects
Research Support, Non-U.S. Gov't - drug effects
Sodium Channel Blockers - drug effects
Sodium Channels - drug effects
Tetrodotoxin - pharmacology

© Med Uni GrazImprint