Clonidine Enhances the Effects of Lidocaine on C-Fiber Action Potential

Abstract

We examined local anesthetic effects of clonidine and its interaction with lidocaine with regard to tonic inhibition of the C-fiber action potential (AP) on the isolated, desheathed rabbit vagus nerve by the sucrose gap method. Clonidine and lidocaine at 500 microM concentrations caused a comparable degree of C-fiber inhibition, corresponding to an AP area under the curve of 75.8% +/- 9.4% (mean +/- SE) and 82.2% +/- 5.9% of control, respectively. Concentrations of clonidine less than 500 microM did not inhibit C-fiber AP. Clonidine, added in concentrations of 500 nM, 500 microM, and 5 mM to a 500 microM lidocaine perfusion, caused a significant decrease in fiber blockade of 18%, 20%, and 54%, respectively, as compared with clonidine added to Locke perfusion (P less than 0.05). The sodium channel blocker tetrodotoxin (3 microM) decreased the AP area to 9.3% +/- 1.3% of control. The remaining tetrodotoxin-resistant AP was almost completely blocked by clonidine (500 microM) and lidocaine (500 microM), indicating a higher susceptibility of tetrodotoxin-resistant fibers to the two drugs than the C-fiber population as a whole. The enhancing effect of a low dose of clonidine (500 nM) on lidocaine-induced (500 microM) inhibition of C-fiber AP might explain the clinical observation that clonidine, at approximately 1000-fold lower concentrations than lidocaine, prolongs the action of lidocaine in peripheral nerve block.

Clonidine prolongs the effect of ropivacaine for axillary brachial plexus blockade

“…4 The effect may occur by direct action of clonidine on nerve fibre conduction, specifically C and A delta fibres. 20,21 However, this would require high local concentrations and would not explain why clonidine alone injected into the nerve sheath failed to produce prolonged analgesia. 18 The action of clonidine would then more likely be via a synergistic mechanism of action in combination with the local anesthetic resulting in the prolonged effect.…”

Clonidine as adjuvant for mepivacaine, ropivacaine and bupivacaine in axillary, perivascular brachial plexus block

“…These factors could have explained the tendency towards a more rapid block onset obtained with ropivacaine. 9,10 It might be speculated that stereospecific factors are involved in the mechanism of action of clonidine on the sodium-channels.…”

A Comparitive Evaluation of 0.75% Ropivacaine With Clonidine and 0.75% Ropivacaine With Dexmedetomidine in Supraclavicular Brachial Plexus Block- A Prospective Randomised Double-Blind Study

“…Among them, ropivacaine is a propyl analogue of bupivacaine, which combines the anaesthetic potency and longer duration of action of bupivacaine with low toxicity profile. 3 The concurrent injection of alpha-2 adrenergic agonist drugs improve the nerve block characteristics of local anaesthetics through either local vasoconstriction 4 and facilitation of C-fibre blockade 5 or spinal action caused by retrograde axonal transport or simple diffusion along the nerve. 6 Clonidine, selective alpha-2 agonist, has been used as an antihypertensive agent.…”