Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents

Alexander M. Binshtok, Peter Gerner, Seog Bae Oh, Michelino Puopolo, Suzuko Suzuki, David P. Roberson, Teri Herbert, Chi Fei Wang, Donghoon Kim, Gehoon Chung, Aya A. Mitani, Ging Kuo Wang, Bruce P. Bean, Clifford J. Woolf

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


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.

Original languageAmerican English
Pages (from-to)127-137
Number of pages11
Issue number1
StatePublished - Jul 2009
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by Alice and Joseph Brooks Fund from Harvard Medical School, Boston, Massachusetts, (to Dr. Oh) and by grant M103KV010015-08K2201-01510 from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Seoul, Republic of Korea (to Dr. Oh). Endo Pharmaceuticals (Chadds Ford, Pennsylvania) has obtained a license to develop this strategy with Harvard Medical School and the Massachusetts General Hospital. This agreement was concluded after completion of this body of work. Drs. Binshtok and Gerner authors contributed equally to this work.


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