PT  - JOURNAL ARTICLE
AU  - Xiaojia Wang
AU  - Cheng Zhou
AU  - Peng Liang
AU  - Jun Yang
AU  - Fengshan Li
AU  - Daqing Liao
AU  - Han Huang
AU  - Jin Liu
TI  - Characterization of Specific Roles of Sodium Channel Subtypes in Regional Anesthesia
AID  - 10.1097/AAP.0000000000000294
DP  - 2015 Sep 01
TA  - Regional Anesthesia & Pain Medicine
PG  - 599--604
VI  - 40
IP  - 5
4099  - http://rapm.bmj.com/content/40/5/599.short
4100  - http://rapm.bmj.com/content/40/5/599.full
SO  - Reg Anesth Pain Med2015 Sep 01; 40
AB  - 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.