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

研究成果: Article

66 引文 (Scopus)

摘要

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.

原文English
頁(從 - 到)127-137
頁數11
期刊Anesthesiology
111
發行號1
DOIs
出版狀態Published - 2009 七月

指紋

Sodium Channel Blockers
Lidocaine
Rodentia
Capsaicin
Nociceptors
Analgesia
QX-314
Sciatic Nerve
Local Anesthesia
Knockout Mice
Reflex

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

引用此文

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 P. ; Woolf, Clifford J. / Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents. 於: Anesthesiology. 2009 ; 卷 111, 編號 1. 頁 127-137.
@article{e3203dda8bef44b192d57605b75ad668,
title = "Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents",
abstract = "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.",
author = "Binshtok, {Alexander M.} and Peter Gerner and Oh, {Seog Bae} and Michelino Puopolo and Suzuko Suzuki and Roberson, {David P.} and Teri Herbert and Wang, {Chi Fei} and Donghoon Kim and Gehoon Chung and Mitani, {Aya A.} and Wang, {Ging Kuo} and Bean, {Bruce P.} and Woolf, {Clifford J.}",
year = "2009",
month = "7",
doi = "10.1097/ALN.0b013e3181a915e7",
language = "English",
volume = "111",
pages = "127--137",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

Binshtok, AM, Gerner, P, Oh, SB, Puopolo, M, Suzuki, S, Roberson, DP, Herbert, T, Wang, CF, Kim, D, Chung, G, Mitani, AA, Wang, GK, Bean, BP & Woolf, CJ 2009, 'Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents', Anesthesiology, 卷 111, 編號 1, 頁 127-137. https://doi.org/10.1097/ALN.0b013e3181a915e7

Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents. / 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 P.; Woolf, Clifford J.

於: Anesthesiology, 卷 111, 編號 1, 07.2009, p. 127-137.

研究成果: Article

TY - JOUR

T1 - Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents

AU - Binshtok, Alexander M.

AU - Gerner, Peter

AU - Oh, Seog Bae

AU - Puopolo, Michelino

AU - Suzuki, Suzuko

AU - Roberson, David P.

AU - Herbert, Teri

AU - Wang, Chi Fei

AU - Kim, Donghoon

AU - Chung, Gehoon

AU - Mitani, Aya A.

AU - Wang, Ging Kuo

AU - Bean, Bruce P.

AU - Woolf, Clifford J.

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

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