Local anaesthetics potentiate epidural or intrathecal opioid analgesia via a poorly defined mechanism. In this study, we have examined the interaction of local anaesthetics (lidocaine, bupivacaine and its optical isomers, tetracaine, procaine and prilocaine) with recombinant μ-, κ-, and δ-opioid receptors expressed in Chinese hamster ovary cells (CHO-μ, κ, and δ, respectively). Lidocaine produced a concentration-dependent displacement of radiolabelled opioid antagonist [3H]diprenorphine ([3H]DPN) binding with the following rank order of inhibitor constant (K(i): κ (210 μM) > μ (552 μM) > δ (1810 μM). Procaine, prilocaine, tetracaine and bupivacaine also displaced [3H]DPN binding in CHO- μ with K(i) values of 244, 204, 43 and 161 μM respectively. Lidocaine produced a concentration-dependent and naloxone-insensitive inhibition of cAMP formation in all cell lines including untransfected cells. Concentration producing 50% inhibition of maximum was μ, 1.32 mM; κ, 2.41 mM; δ, 1.27 mM; untransfected, 2.78 mM. When lidocaine (300 μM) was co-incubated with spiradoline (κ-selective) and [D-Ala2, MePhe4, Gly(ol)5] enkephalin (DAMGO μ-selective) in CHO-κ and μ cells we did not observe an additive interaction for cAMP formation. In contrast, there was an apparent inhibitory action of the combination at the κ receptor. This study suggests that clinical concentrations of local anaesthetics interact with μ and κ but not δ opioid receptors. As there was no synergism between local anaesthetics and opioids we suggest that the interaction of these agents in the clinical setting does not occur at the cellular level.
- Anaesthetics local
- Measurement techniques, radioligand binding
- Metabolism, cAMP
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine