Journalartikel

Jahr der Veröffentlichung: 2009

Seiten: 258-264

Zeitschrift: Anesthesia & Analgesia

Bandnummer: 109

Heftnummer: 1

ISSN: 0003-2999

Open Access Status: Bronze

DOI Link: https://doi.org/10.1213/ane.0b013e3181a3d5d8

Verlag: Lippincott, Williams & Wilkins

Abstract: 

BACKGROUND: Spinal sensitization and facilitatory processes in dorsal horn neurons after nerve injury alter spinal outflow leading to enhanced pain perception and chronic pain syndromes. Clinically used Na+ channel blockers at doses which do not block conduction can relieve such chronic pain. Although much attention has been paid to their effect upon afferents, less work has been done with their effect on the excitability of central sensory neurons. Thus, we investigated the effects of the Na+ channel blockers mexiletine and lidocaine on sensory spinal dorsal horn neurons.

METHODS: Patch-clamp recordings were directly performed in visualized neurons of the substantia gelatinosa in the spinal cord of young rats to investigate the effect of mexiletine and lidocaine in different types of dorsal horn neurons (tonically firing, adapting-firing, and single spike neurons).

RESULTS: All three different types of neurons responded dose-dependently to mexiletine and lidocaine. Both local anesthetics reversibly inhibited Na+ and K+ currents. The half-maximal inhibitory concentration for Na+ conductance block was 89 +/- 2 or 54 +/- 6 mu M and for delayed-rectifier K+ conductance block was 582 36 or 398 +/- 14 mu M for liclocaine and mexiletine, respectively. The inhibition of Na+ and K+ currents consecutively altered the properties of single action potentials and reduced the firing rate of tonically firing and adapting-firing neurons.

CONCLUSIONS: In clinically relevant concentrations, liclocaine and mexiletine reduced the excitability of sensory dorsal horn neurons via a blockade of Na+ and K+ channels. Our work confirms that, in addition to the peripheral effects of liclocaine and mexiletine, modulation of voltage-gated ion channels in the central nervous system contributes to the antinociceptive effects of these drugs used in pain therapy. (Anesth Analg 2009;109:258-64)

Harvard-Zitierstil: Olschewski, A., Schnoebel-Ehehalt, R., Li, Y., Tang, B., Braeu, M. and Wolff, M. (2009) Mexiletine and Lidocaine Suppress the Excitability of Dorsal Horn Neurons, Anesthesia & Analgesia, 109(1), pp. 258-264. https://doi.org/10.1213/ane.0b013e3181a3d5d8

APA-Zitierstil: Olschewski, A., Schnoebel-Ehehalt, R., Li, Y., Tang, B., Braeu, M., & Wolff, M. (2009). Mexiletine and Lidocaine Suppress the Excitability of Dorsal Horn Neurons. Anesthesia & Analgesia. 109(1), 258-264. https://doi.org/10.1213/ane.0b013e3181a3d5d8