Toxicity Effects of Lidocaine and Bupivacaine on Human Intervertebral Disc Cells in Vitro
Authors: Gradisnik L. , Velnar T. , Bunc G. , Rupnik M. Slak 
Published: May 2014

Introduction The treatment and diagnostics of discogenic low back pain often employs local anesthetic agents. Lidocaine and bupivacaine are most commonly used for controlling and relieving the pain in interventional spine procedures. It is known that these local anaesthetics may be cytotoxic to the intervertebral disc cells following the intradiscal injections and that they may provoke or accelerate the intervertebral disc degeneration. However, the potential deletorious effects of these agents to human cells still remain unclear, as studies so far have been predominantly performed on animal cells. The aim of the study was to evaluate the effect of various local anaesthetics on human intervertebral disc cells in vitro and to compare the cytotoxicity of lidocaine, bupivacaine, and mixture of both anaesthetics to saline solution control. Materials and Methods Annulus fibrosus and nucleus pulposus cells were isolated from human lumbar intervertebral disc fragments following discectomies. They were cultured in the microtiter plates and exposed to various concentrations of lidocaine, bupivacaine, as well as their mixture. The saline solution was used as a control. Three different dilutions (undiluted, 1:2 and 1:4) of anesthetic agents were tested. The cells were treated for 6, 24, and 48 hours. They were then examined with the crystal violet cell staining to determine the fraction of cells surviving the treatment. Results Human intervertebral disc cells demonstrated a time- and dose-dependent toxicity to lidocaine and bupivacaine. Nulceus pulposus cells were more susceptible than AF cells to the toxic effects of both anesthetic agents. Lidocaine was the more toxic in all three tested concentrations with the final cell survival fraction of 0, 10, and 20%, respectively. Bupivacaine presented less cytotoxicity than lidocaine with the final survival of 10, 60, and 80%, respectively. Lidocaine-bupivacaine mixture showed an intermediate toxicological effect. The cell death was mainly caused by necrosis rather than apoptosis. Conclusion When incubating the human intervertebral disc cells in vitro with a combination of anesthetic agents commonly used for discography, the cytotoxic effects were observed in a dose- and time-dependent manner. According to our study, lidocaine and its mixtures should be avoided due to its high toxicity to the intervertebral disc cells. Bupivacaine was less toxic, especially when used in 1:4 dilutions and may be thus recommended for the intradiscal diagnostics. It is assumed that the genesis of disc degeneration might be contributed also by the toxic effects of the anaesthetics used, culminating to progressive tissue damage after the diagnostic measures. Disclosure of Interest None declared References Carragee EJ, Hannibal M. Diagnostic evaluation of low back pain. Orthop Clin North Am 2004;35(1):7–16 Lee H, Sowa G, Vo N, et al. Effect of bupivacaine on intervertebral disc cell viability. Spine J 2010;10(2):159–166 Rahnama R, Wang M, Dang AC, Kim HT, Kuo AC. Cytotoxicity of local anesthetics on human mesenchymal stem cells. J Bone Joint Surg Am 2013;95(2):132–137