• Isao Tsuneyoshi, Toyoaki Maruta, Takayuki Nemoto, Shinya Satoh, Tasuku Kanai, Toshihiko Yanagita, and Akihiko Wada.
• Department of Anesthesiology, Miyazaki Medical College, University of Miyazaki, Miyazaki 889-1692, Japan. mmctm2@yahoo.co.jp
• J Anesth. 2011 Aug 1;25(4):549-57.

PurposeBesides being administered systemically for sedation and analgesia, α(2)-agonists such as dexmedetomidine and clonidine have been administered with intrathecal, epidural, or perineural injections, leading to an antinociceptive effect at the spinal cord or peripheral nerve level. However, the mechanism for this remains unclear. In the present study, we examined whether dexmedetomidine and clonidine could inhibit the function of tetrodotoxin-sensitive Na(+) channels, which play important roles in the generation of pain.MethodsCultured bovine adrenal chromaffin cells expressing the tetrodotoxin-sensitive Na(v)1.7 Na(+) channel isoform were incubated in KRP buffer containing 2 μCi (22)NaCl for 5 min without or with dexmedetomidine or clonidine in the absence or presence of veratridine, α-scorpion venom, β-scorpion venom, Ptychodiscus brevis toxin-3 or ouabain. Cells were then washed and counted radioactively.ResultsDexmedetomidine and clonidine reduced veratridine-induced (22)Na(+) influx via Na(v)1.7 in a concentration-dependent manner (EC(50) = 50 μM and 530 μM), even in the presence of ouabain, an inhibitor of Na(+), K(+)-ATPase. Dexmedetomidine and clonidine shifted the concentration-response curve of veratridine for (22)Na(+) influx downward without altering the EC(50) of veratridine. Atipamezole and yohimbine, α(2)-antagonists, did not prevent the inhibition of veratridine-induced (22)Na(+) influx by dexmedetomidine. Dexmedetomidine and clonidine combined with lidocaine induced more inhibition of veratridine-induced (22)Na(+) influx than each drug did individually. Atipamezole and yohimbine did not prevent the lidocaine-enhancing effect of dexmedetomidine and clonidine.ConclusionDexmedetomidine and clonidine inhibit the function of Na(v)1.7 independent of α(2)-adrenoceptor. These results may lead to a deeper understanding of the peripheral antinociceptive effects of α (2)-agonists.

42 keywords...

hide…