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ANESTHETIC PHARMACOLOGY

The Effects of Local and Intravenous Anesthetics on Recombinant Rat VR1 Vanilloid Receptors

Kazuyoshi Hirota, MD^*, Darren Smart, PhD, and David G. Lambert, PhD

*Department of Anesthesiology, University of Hirosaki School of Medicine, Japan; Neurology-CEDD, GlaxoSmithKline, Essex; and University Department of Anaesthesia, Critical Care and Pain Management, Leicester Royal Infirmary, United Kingdom

Address correspondence and reprint requests to David G. Lambert, PhD, University Department of Anesthesia, Critical Care and Pain Management, Leicester Royal Infirmary, Leicester, LE1 5WW, UK. Address e-mail to DGL3{at}le.ac.uk

Capsaicin, acting at the vanilloid 1 receptor (VR1), may potentiate local anesthetic activity, and as a ligand-gated ion channel of the transient receptor potential family, may also be a target for IV general anesthetics. We have examined whether local (lidocaine, prilocaine, and procaine 0.1–10 mM; 10 mM represents 0.25%–0.27% wt/vol) or IV anesthetics (propofol 10 µM, thiopental 100 µM, and ketamine 100 µM) interact with recombinant rat VR1 expressed in human embryonic kidney (HEK293) cells (VR1-HEK293). We have assessed receptor interaction functionally by monitoring intracellular Ca²⁺ ([Ca²⁺]_i) in Fura2-loaded cells at 37°C. The addition of capsaicin (60 nM) produced a time-dependent biphasic increase in [Ca²⁺]_i amounting to 50–100 nM above than basal, which was inhibited by capsazepine 10 µM and was absent in wild type HEK293 cells. Lidocaine and prilocaine alone (e.g., at 10 mM) significantly increased [Ca²⁺]_i by 67 ± 6 nM and 33 ± 7 nM, respectively, and concentration-dependently inhibited the capsaicin response. The effects of procaine were obscured by anesthetic-induced quenching of Fura2. In wild type HEK293 cells, lidocaine (10 mM) alone produced a small increase in [Ca²⁺]_i. All IV anesthetics failed to modify capsaicin-increased [Ca²⁺]_i. In conclusion, the present data suggest that local but not IV general anesthetics interact with recombinant rat VR1 receptors with the former anesthetics having antagonistic activity.

IMPLICATIONS: Vanilloid receptors (VR1) are activated by capsaicin, the pain-producing component of hot chili peppers. We suggest that local (but not IV general) anesthetics may have inhibitory actions on this receptor.

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