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Characterization of Specific Roles of Sodium Channel Subtypes in Regional Anesthesia
  1. Xiaojia Wang, MD*,,
  2. Cheng Zhou, PhD*,
  3. Peng Liang, MD,
  4. Jun Yang, PhD*,
  5. Fengshan Li, MB*,,
  6. Daqing Liao, MB*,
  7. Han Huang, MD*,§ and
  8. Jin Liu, MD*,
  1. From the *Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, and †Department of Anesthesiology, West China Hospital of Sichuan University; ‡State Key Laboratory of Biotherapy, Sichuan University; and §Department of Anesthesiology, West China Second Hospital of Sichuan University, Sichuan, People’s Republic of China
  1. Address correspondence to: Jin Liu, MD, Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center and Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China (e-mail: scujinliu{at}gmail.com) and Han Huang, MD, Department of Anesthesiology, West China Second Hospital of Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China (e-mail: huanghan1981{at}gmail.com).

Abstract

Background and Objectives Commonly used local anesthetics (eg, lidocaine) are nonselective in blocking sodium channel subtypes, potentially resulting in adverse events, such as prolonged muscle paralysis and unstable hemodynamics. Subtype-selective sodium channel block might avoid these unwanted adverse effects while preserving desirable anesthetic effects. The contributions of sodium channel subtypes in different components of regional anesthesia are unclear and this study assumed that selective sodium channel subtype block might produce selective nerve block.

Methods Sciatic nerve block was performed in mice with lidocaine (nonselective sodium channel blocker), tetrodotoxin (TTX, TTX-sensitive sodium channel blocker), and A-803467 (selective Nav1.8 subtype blocker). Tactile sensory, pinprick, and thermal sensory block as well as motor block were evaluated after injection of study drugs. Median effective concentration (EC50) of lidocaine, TTX, and A-803467 as well as their blocking durations were determined.

Results Lidocaine produced regional anesthetic effects including tactile, pinprick, and thermal sensory block as well as motor block, with EC50 [mean, 95% confidence intervals (CIs)] of 4.4 (3.7–5.2), 9.4 (8.0–10.9), 5.2 (4.3–6.2), and 3.7 (3.3–4.2) mmol/L, respectively. Tetrodotoxin produced tactile sensory block and motor block with EC50 (mean, 95% CIs) of 7.7 (6.0–11.0) and 8.3 (7.4–9.8) μmol/L, respectively; whereas A-803467 produced tactile sensory block only, with EC50 (mean, 95% CIs) of 12.6 (11.7–15.6) μmol/L.

Conclusions Sodium channel subtype selective blockers could induce selective nerve blocks. Tetrodotoxin-sensitive sodium channel subtypes contribute to low-threshold sensory block (eg, tactile) and motor block. Unexpectedly, selective Nav1.8 subtype block induced low-threshold sensory block rather than nociceptive or motor block.

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Footnotes

  • The authors declare no conflict of interest.

    This study was supported by grant 81401139 (to Dr Cheng Zhou) and grant 81401623 (to Dr Han Huang) from the National Natural Science Foundation of China; and the grant from the National Major Scientific and Technological Special Project (2014ZX09101001-004) for Significant New Drugs Development (to Dr Jin Liu).

    Xiaojia Wang and Cheng Zhou contributed equally to this study.

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