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Background: Nociceptive-selective local anesthesia is pro-duced by entry of the permanently charged lidocaine-derivative QX-314 into nociceptors when coadministered with capsaicin, a transient receptor potential vanilloid 1 (TRPV1) channel ago-nist. However, the pain evoked by capsaicin before establish-ment 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