Clonidine Prolongation of Lidocaine Analgesia after Sciatic Nerve Block in Rats Is Mediated via the Hyperpolarization-activated Cation Current, Not by α-Adrenoreceptors
Open Access
- 1 August 2004
- journal article
- laboratory investigations
- Published by Ovid Technologies (Wolters Kluwer Health) in Anesthesiology
- Vol. 101 (2), 488-494
- https://doi.org/10.1097/00000542-200408000-00031
Abstract
Background Although clonidine is commonly combined with local anesthetics to extend duration of peripheral nerve block, the mechanism by which clonidine potentiates local anesthetic action in vivo is unclear. Methods Male Sprague-Dawley rats received percutaneous injections of 1% lidocaine with/without clonidine or epinephrine into the sciatic notch and duration of sensory blockade was quantified by inhibition of pinprick foot withdrawal. The antagonists prazosin or yohimbine were injected before lidocaine with clonidine or epinephrine to determine the role of alpha-adrenergic receptors. The role of the hyperpolarization-activated cation current (Ih) was evaluated by injecting the current blocker ZD 7288 as well as the current enhancers forskolin and 8-Br-cAMP before lidocaine alone or with 15 micrograms/ml clonidine. Results Mean duration of sensory block for lidocaine alone was 69 +/- 2 min. Sensory block duration increased monotonically with increasing doses of added clonidine or epinephrine. Preinjection of prazosin but not yohimbine prevented the increase in block duration seen with epinephrine. Neither alpha-adrenergic antagonist attenuated the extended duration of block with clonidine. ZD 7288 extended sensory blockade equivalent to the prolongation observed with clonidine. There was no additive effect when ZD 7288 and clonidine were combined, and a decreased duration of nerve block when either forskolin or 8-Br-cAMP preceded injection of lidocaine with clonidine. Conclusions The findings indicate that prolongation of duration of in vivo lidocaine nerve blockade by clonidine is not mediated by an alpha-adrenergic mechanism but likely involves the Ih current.Keywords
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