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

Abstract

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.

Dexmedetomidine and clonidine inhibit the function of NaV1.7 independent of α2-adrenoceptor in adrenal chromaffin cells

“…current by the a 2 -agonists differed depending on the type of Na ? channel or nerve [9,[35][36][37][38][39]. The IC 50 of dexmedetomidine for the tetrodotoxin-sensitive Na V 1.7 current in our present study was similar to that for the tetrodotoxin-resistant Na ?…”

“…The IC 50 of dexmedetomidine for the tetrodotoxin-sensitive Na V 1.7 current in our present study was similar to that for the tetrodotoxin-resistant Na ? current in rat DRG neurons (58 lM) and the compound action potential in dog stellate ganglia (71.6 lM) [9,35]. On the other hand, the IC 50 of clonidine for the tetrodotoxin-sensitive Na V 1.7 current in our present study was greater than that for the tetrodotoxinresistant Na ?…”

“…current or an action potential combining the tetrodotoxinsensitive and tetrodotoxin-resistant Na ? currents is inhibited by a 2 -agonists [9,[35][36][37][38][39]. However, the effect of a 2 -agonists on the tetrodotoxin-sensitive Na ?…”

“…A recent study reported that a 2 -agonists directly inhibited tetrodotoxin-resistant Na ? channels in rat DRG neurons [9]. However, it remains unclear whether a 2 -adrenoceptor agonists can inhibit the function of tetrodotoxin-sensitive Na ?…”

“Above All, Do No Harm”

“…6,7 Laboratory studies using clonidine have been limited to examining its efficacy in combination with short-acting drugs such as lidocaine or procaine. The effect of clonidine added to a long-acting local anesthetic (bupivacaine, levobupivacaine, and ropivacaine) for peripheral nerve blocks has not been studied in vitro, whereas results in human studies have been mixed.…”