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Hyperalgesia by low doses of the local anesthetic lidocaine involves cannabinoid signaling: An fMRI study in mice


Bosshard, Simone C; Grandjean, Joanes; Schroeter, Aileen; Baltes, Christof; Zeilhofer, Hanns U; Rudin, Markus (2012). Hyperalgesia by low doses of the local anesthetic lidocaine involves cannabinoid signaling: An fMRI study in mice. Pain, 153(7):1450-1458.

Abstract

Lidocaine is clinically widely used as a local anesthetic inhibiting propagation of action potentials in peripheral nerve fibers. Correspondingly, the functional magnetic resonance imaging (fMRI) response in mouse brain to peripheral noxious input is largely suppressed by local lidocaine administered at doses used in a clinical setting. We observed, however, that local administration of lidocaine at doses 100 × lower than that used clinically led to a significantly increased sensitivity of mice to noxious forepaw stimulation as revealed by fMRI. This hyperalgesic response could be confirmed by behavioral readouts using the von Frey filament test. The increased sensitivity was found to involve a type 1 cannabinoid (CB(1)) receptor-dependent pathway as global CB(1) knockout mice, as well as wild-type mice pretreated systemically with the CB(1) receptor blocker rimonabant, did not display any hyperalgesic effects after low-dose lidocaine. Additional experiments with nociceptor-specific CB(1) receptor knockout mice indicated an involvement of the CB(1) receptors located on the nociceptors. We conclude that low concentrations of lidocaine leads to a sensitization of the nociceptors through a CB(1) receptor-dependent process. This lidocaine-induced sensitization might contribute to postoperative hyperalgesia.

Abstract

Lidocaine is clinically widely used as a local anesthetic inhibiting propagation of action potentials in peripheral nerve fibers. Correspondingly, the functional magnetic resonance imaging (fMRI) response in mouse brain to peripheral noxious input is largely suppressed by local lidocaine administered at doses used in a clinical setting. We observed, however, that local administration of lidocaine at doses 100 × lower than that used clinically led to a significantly increased sensitivity of mice to noxious forepaw stimulation as revealed by fMRI. This hyperalgesic response could be confirmed by behavioral readouts using the von Frey filament test. The increased sensitivity was found to involve a type 1 cannabinoid (CB(1)) receptor-dependent pathway as global CB(1) knockout mice, as well as wild-type mice pretreated systemically with the CB(1) receptor blocker rimonabant, did not display any hyperalgesic effects after low-dose lidocaine. Additional experiments with nociceptor-specific CB(1) receptor knockout mice indicated an involvement of the CB(1) receptors located on the nociceptors. We conclude that low concentrations of lidocaine leads to a sensitization of the nociceptors through a CB(1) receptor-dependent process. This lidocaine-induced sensitization might contribute to postoperative hyperalgesia.

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4 citations in Web of Science®
5 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:570 Life sciences; biology
170 Ethics
610 Medicine & health
Language:English
Date:2012
Deposited On:20 Dec 2012 08:11
Last Modified:05 Apr 2016 16:12
Publisher:Elsevier
ISSN:0304-3959
Publisher DOI:https://doi.org/10.1016/j.pain.2012.04.001
PubMed ID:22575227

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