Mechanisms of Lidocaines Action on Subtypes of Spinal Dorsal Horn Neurons Subject to the Diverse Roles of Na+ and K+ Channels in Action Potential Generation

Wolff, Matthias Dr. med; Schnöbel-Ehehalt, Rose Dr. med; Mühling, Jörg Dr. med; Weigand, Markus A. Dr. med; Olschewski, Andrea Dr. med

doi: 10.1213/ANE.0000000000000280
Pain and Analgesic Mechanisms: Research Report

BACKGROUND: Superficial dorsal horn neurons of the spinal cord receive sensory information from Aδ and C fibers. According to their response to sustained depolarization, these cells can be divided into 3 groups: tonic (TFN), adapting (AFN), and single spike firing (SSN) neurons. During spinal and systemic administration of lidocaine, these neurons are exposed to different concentrations of the local anesthetic lidocaine. In this study, we explored its effect on the excitability of sensory neurons.

METHODS: Whole-cell patch-clamp recordings from dorsal horn neurons of Wistar rats were used to study the action of lidocaine on firing properties. To estimate the impact of a blockade of voltage-gated potassium channels by lidocaine (100 μM) on the firing properties of different neurons, the sodium and potassium channel inhibition of lidocaine was investigated in the light of the effects of tetrodotoxin (TTX, 10 nM) and tetraethylammonium (10 mM). For statistical analysis, the Wilcoxon matched-pairs signed rank test was used throughout.

RESULTS: All 3 types of neurons responded to lidocaine with changes in the shape of their action potentials. The peak amplitude of the single action potentials was decreased (P = 0.031, P = 0.013, and P = 0.014 for SSN, AFN, and TFN neurons, respectively), and the duration of the action potentials was increased (P = 0.016, P = 0.032, and P = 0.031 for SSN, AFN, and TFN neurons, respectively). The maximum positive slope (P = 0.016 and P = 0.0010 for SSN and AFN, respectively) and the negative slope (P = 0.016, P = 0.0025, and P = 0.020 for SSN, AFN, and TFN neurons, respectively) decreased after application of lidocaine. In tonically firing neurons, lidocaine reduced the repetitive firing (P = 0.0016), and this effect was mimicked by a combination of TTX and tetraethylammonium. In AFN, TTX mimicked the action of lidocaine.

CONCLUSIONS: Lidocaine at low concentrations suppresses tonic firing neurons by interacting with voltage-gated potassium channels. The effects on adapting firing neurons can be explained by an interaction with voltage-gated sodium channels. In contrast, the firing pattern of SSN is not affected at the administered concentrations. This different sensitivity to low concentrations of sodium and particularly of potassium channel blockers might represent a novel approach for a differentiated blockade of different spinal dorsal horn neurons.

Published ahead of print June 3, 2014.

From the Department of Anesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University, Giessen, Germany.

Andrea Olschewski, Dr. med, is currently affiliated with Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.

Accepted for publication March 2, 2014.

Published ahead of print June 3, 2014.

Funding: Matthias Wolff was supported by the Justus Liebig University Giessen A.O. was supported by the Justus Liebig University Giessen as well as by the DFG (SFB 547 “Kardiopulmonales Gefäßsystem).

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Matthias Wolff, PD, Dr. med, Department of Anesthesiology, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University, Rudolf-Buchheim-Straße 7, 35392 Giessen, Germany. Address e-mail to matthias.wolff@physiologie.med.uni-giessen.de.

© 2014 International Anesthesia Research Society