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Effects of α2-adrenoceptor agonists on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglion neurons*

Published online by Cambridge University Press:  01 November 2007

A. Oda ,
H. Iida ,
S. Tanahashi ,
Y. Osawa ,
S. Yamaguchi  and
S. Dohi
A. Oda
Affiliation:
Gifu UniversityGraduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu, Japan
H. Iida*
Affiliation:
Gifu UniversityGraduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu, Japan
S. Tanahashi
Affiliation:
Gifu UniversityGraduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu, Japan
Y. Osawa
Affiliation:
Gifu UniversityGraduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu, Japan
S. Yamaguchi
Affiliation:
Gifu UniversityGraduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu, Japan
S. Dohi
Affiliation:
Gifu UniversityGraduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu, Japan
*
Correspondence to: Hiroki Iida, Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan. E-mail: iida@cc.gifu-u.ac.jp; Tel: +81 58 230 6404; Fax: +81 58 230 6405
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Summary

Background and objective

When intrathecally or epidurally administered, α2-adrenoceptor agonists produce potent antinociception by affecting the activity of primary afferent fibres and spinal cord neurons. Recent reports have indicated that in dorsal root ganglion neurons, tetrodotoxin-resistant Na+ channels play important roles in the conduction of nociceptive sensation. We therefore investigated the effects of α2-adrenoceptor agonists on tetrodotoxin-resistant Na+ currents.

Methods

Using the whole-cell patch-clamp technique, we recorded tetrodotoxin-resistant Na+ currents from rat dorsal root ganglion neurons.

Results

Both clonidine and dexmedetomidine reduced the peak amplitude of the tetrodotoxin-resistant Na+ current concentration- and use-dependently. The concentration required for a half-maximal effect was significantly lower for dexmedetomidine (58.0 ± 10.2 μmol) than for clonidine (257.2 ± 30.9 μmol) at holding potential −70 mV. The current inhibitions induced by these agonists were not prevented by 1 μmol yohimbine, an α2-adrenoceptor antagonist. Both clonidine and dexmedetomidine shifted the inactivation curve for the tetrodotoxin-resistant Na+ current in the hyperpolarizing direction. The combinations clonidine with lidocaine and dexmedetomidine with lidocaine produced an additive blockade-type interaction on the tetrodotoxin-resistant Na+ current.

Conclusions

The results suggest that a direct inhibition of tetrodotoxin-resistant Na+ channels may contribute to the antinociceptive effects of clonidine and dexmedetomidine when used as additives to regional anaesthesia.

Keywords

ION CHANNELSSODIUM CHANNELSANAESTHESIA GENERAL, mechanism of actions of anaestheticsADRENERGIC ALPHA AGONISTS, dexmedetomidine, clonidine
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 24 , Issue 11 , November 2007 , pp. 934 - 941
Copyright
Copyright © European Society of Anaesthesiology 2007

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Footnotes

*

Presented in part at the annual meeting of the International Anesthesia Research Society, Ft. Lauderdale, Florida, USA (2001).

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