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Binshtok, Alexander M.,Gerner, Peter,Oh, Seog Bae,Puopolo, Michelino,Suzuki, Suzuko,Roberson, David P.,Herbert, Teri,Wang, Chi-Fei,Kim, Donghoon,Chung, Gehoon,Mitani, Aya A.,Wang, Ging Kuo,Bean, Bruce American Society of Anesthesiologists, Inc. 2009 Anesthesiology Vol.111 No.1
BACKGROUND:: Nociceptive-selective local anesthesia is produced by entry of the permanently charged lidocaine-derivative QX-314 into nociceptors when coadministered with capsaicin, a transient receptor potential vanilloid 1 (TRPV1) channel agonist. However, the pain evoked by capsaicin before establishment of the QX-314–mediated block would limit clinical utility. Because TRPV1 channels are also activated by lidocaine, the authors tested whether lidocaine can substitute for capsaicin to introduce QX-314 into nociceptors through TRPV1 channels and produce selective analgesia. METHODS:: Lidocaine (0.5% [17.5 mm], 1% [35 mm], and 2% [70 mm]) alone, QX-314 (0.2% [5.8 mm]) alone, and a combination of the two were injected subcutaneously and adjacent to the sciatic nerve in rats and mice. Mechanical and thermal responsiveness were measured, as was motor block. RESULTS:: Coapplication of 0.2% QX-314 with lidocaine prolonged the nociceptive block relative to lidocaine alone, an effect attenuated in TRPV1 knockout mice. The 0.2% QX-314 alone had no effect when injected intraplantary or perineurally, and it produced only weak short-lasting inhibition of the cutaneous trunci muscle reflex. Perisciatic nerve injection of lidocaine with QX-314 produced a differential nociceptive block much longer than the transient motor block, lasting 2 h (for 1% lidocaine) to 9 h (2% lidocaine). Triple application of lidocaine, QX-314, and capsaicin further increased the duration of the differential block. CONCLUSIONS:: Coapplication of lidocaine and its quaternary derivative QX-314 produces a long-lasting, predominantly nociceptor-selective block, likely by facilitating QX-314 entry through TRPV1 channels. Delivery of QX-314 into nociceptors by using lidocaine instead of capsaicin produces sustained regional analgesia without nocifensive behavior.