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REGIONAL ANESTHESIA AND PAIN MEDICINE

Characteristics of Ropivacaine Block of Na+ Channels in Rat Dorsal Root Ganglion Neurons

Akiyoshi Oda, MD^*, Hidenori Ohashi, DVM, PhD, Seiichi Komori, DVM, PhD, Hiroki Iida, MD, PhD^*, and Shuji Dohi, MD, PhD^*

*Department of Anesthesiology and Critical Care Medicine, and Laboratory of Pharmacology, Veterinary Science, Faculty of Agriculture, Gifu University, Gifu City, Gifu, Japan

Address correspondence and reprint requests to Shuji Dohi, MD, PhD, Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu City, Gifu 500-8705, Japan. Address e-mail to shu-dohi{at}cc.gifu-u.ac.jp

When used for epidural anesthesia, ropivacaine can produce a satisfactory sensory block with a minor motor block. We investigated its effect on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na⁺ currents in rat dorsal root ganglion (DRG) neurons to elucidate the mechanisms underlying the above effects. Whole-cell patch-clamp recordings were made from enzymatically dissociated neurons from rat DRG. A TTX-S Na⁺ current was recorded preferentially from large DRG neurons and a TTX-R Na⁺ current preferentially from small ones. Ropivacaine shifted the activation curve for the TTX-R Na⁺ channel in the depolarizing direction and the inactivation curve for both types of Na⁺ channel in the hyperpolarizing direction. Ropivacaine blocked TTX-S and TTX-R Na⁺ currents, but its half-maximum inhibitory concentration (IC₅₀) was significantly lower for the latter current (116 ± 35 vs 54 ± 14 µM; P < 0.01); similar IC₅₀ values were obtained with the (R)-isomer of ropivacaine. Ropivacaine produced a use-dependent block of both types of Na⁺ channels. Ropivacaine preferentially blocks TTX-R Na⁺ channels over TTX-S Na⁺ channels. We conclude that because TTX-R Na⁺ channels exist mainly in small DRG neurons (which are responsible for nociceptive sensation), such selective action of ropivacaine could underlie the differential block observed during epidural anesthesia with this drug.

Implications: Whole-cell patch-clamp recordings of tetrodotoxin-sensitive and tetrodotoxin-resistant Na⁺ currents in rat dorsal root ganglion neurons showed ropivacaine preferentially blocked tetrodotoxin-resistant Na⁺ channels over tetrodotoxin-sensitive Na⁺ channels. This could provide a desirable differential sensory blockade during epidural anesthesia using ropivacaine.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999