Bupivacaine—the deadly friend of intervertebral disc cells?

Quero, Lilian; Klawitter, Marina; Nerlich, Andreas G.; Leonardi, M.C.; Boos, Norbert; Wuertz, Karin

doi:10.1016/j.spinee.2010.11.001

Cited by 36 publications

(39 citation statements)

References 22 publications

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“…Animal studies confirmed that needle puncture and pressure cause IVD degeneration [6]–[8]. In addition, in vitro studies showed that bupivacaine [2], [9], [10] and the contrast agent iopamidol [6] have toxic effects on IVD cells in vitro .…”

Section: Introductionmentioning

confidence: 90%

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Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

et al. 2014

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BackgroundDiscography and discoblock are imaging procedures used to diagnose discogenic low back pain. Although needle puncture of the intervertebral disc (IVD) itself induces disc degeneration, the agents used in these procedures may also have harmful effects on IVD cells. The purpose of this study was to analyze whether radiocontrast agents and local anesthetic agents have detrimental effects on human nucleus pulposus (NP) cells.MethodsHealthy human NP cells were cultured for 7 days in three-dimensional (3D) cell–alginate bead composites, and were then exposed to clinically relevant doses of a radiocontrast agent (iotrolan) or local anesthetic (lidocaine or bupivacaine). Cell viability and apoptosis were measured by confocal microscopy and flow cytometry. On the basis of caspase expression profiles, the apoptotic pathways activated by the agents were identified by Western blot analysis.ResultsThe radiocontrast agent iotrolan did not affect NP cell viability or induce apoptosis. In contrast, both the anesthetic agents significantly decreased cell viability and increased the apoptotic cell number in a time- and dose-dependent manner. After 120 min, 2% lidocaine and 0.5% bupivacaine decreased percent live cells to 13% and 10%, respectively (p<0.05). The number of apoptotic cells was doubled by increasing lidocaine dosage from 1% to 2% (23% and 42%) and bupivacaine from 0.25% to 0.50% (25% and 48%) (p<0.05). Western blot analysis revealed that both anesthetic agents upregulated cleaved caspase-3 and caspase-8, whereas only bupivacaine upregulated cleaved caspase-9.Conclusions/SignificanceThe present study demonstrates that iotrolan does not affect the viability of healthy human NP cells. In contrast, the two anesthetic agents commonly used in discography or discoblock may cause extensive damage to IVDs by inducing apoptotic cell death.

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Section: Introductionmentioning

confidence: 90%

“…Provocative discography is an imaging procedure routinely used to diagnose discogenic LBP on the basis of the level of pain induced by the injection of radiocontrast agents [2]. A needle is inserted into the nucleus pulposus (NP) under fluoroscopic guidance and a radiocontrast agent is injected to the center of the painful IVD.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

et al. 2014

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“…Viability measurement Cellular viability after treatment with different concentrations of TPL (6, 18 and 30 h) was analyzed using the MTT assay as previously described, which has also been shown to be comparable to other viability/toxicity measurements (Picogreen assay, cell counting) [22]. Non-toxic concentrations were chosen for subsequent experiments.…”

Section: Methodsmentioning

confidence: 99%

Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1β treated human intervertebral disc cells

et al. 2011

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Introduction Increased levels of proinflammatory cytokines seem to play a pivotal role in the development of back pain in a subpopulation of patients with degenerative intervertebral disc (IVD) disease. As current treatment options are mostly limited to surgical interventions or conservative treatment, anti-inflammatory substances might offer a novel, more target-orientated therapeutic approach. Triptolide (TPL), a natural substance found in the Chinese medicinal herb Tripterygium wilfordii Hook, has been demonstrated to possess anti-inflammatory effects in various cells, but no studies exist so far for the IVD. Therefore, the aim of this study was to determine the effects of TPL on human IVD cells by analyzing changes in gene expression and underlying molecular mechanisms. Materials and methods In order to investigate the antiinflammatory, anabolic and anti-catabolic effect of TPL, dose-dependency experiments (n = 5) and time course experiments (n = 5) were performed on IL-1b prestimulated human IVD cells and changes in gene expression of IL-6/-8, TNF-a, PGE2S, MMP1/2/3/13, aggrecan and collagen-I/-II were analyzed by real-time RT-PCR. The molecular mechanisms underlying the effects observed upon TPL treatment were investigated by analyzing involvement of Toll-like receptors TLR2/4 (real-time RT-PCR, n = 5), NF-jB, MAP kinases p38, ERK and JNK (immunoblotting and immunocytochemistry, n = 4) as well as RNA polymerase II (immunoblotting, n = 3). Results Results showed that 50 nM TPL exhibited an anti-inflammatory, anti-catabolic and anabolic effect on the mRNA level for IL-6/-8, PGE2S, MMP1/2/3/13, aggrecan, collagen-II and TLR2/4, with most pronounced changes after 18 h for proinflammatory cytokines and MMPs or 30 h for TLRs and matrix proteins. However, we also observed an up-regulation of TNF-a at higher concentrations. The effects of TPL did not seem to be mediated via an inhibition of NF-jB or a decrease of RNA polymerase II levels, but TPL influenced activity of MAP kinases p38 and ERK (but not JNK) and expression of TLR2/4. Conclusions In conclusion, TPL may possess promising potential for the treatment of inflammation-related discogenic back pain in vitro, but its analgetic effect will need to be confirmed in an appropriate in vivo animal model.

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“…Da Diskografie ein invasives, teilweise schmerzhaftes Verfahren ist mit möglichen Komplikationen wie z. B. Infektion oder gewebetoxischer Bandscheibenschädigung [10][11], sollte CT-Diskografie nicht standardmäßig erfolgen und erfordert eine enge Indikationsstellung. Upright-MRT und CT-Myelografie bieten hier eine Alternative, um die Schädigung einer gesunden Bandscheibe zu vermeiden.…”

Section: Stellenwert Der Ct-diskografie Bei Unklarer Radikulopathieunclassified

“…Besonders gerechtfertigt ist sie aber ob des sowohl diagnostischen als auch therapeutischen Wertes von Infiltrationen an der Wirbelsäule im Rahmen einer ohnehin indizierten interventionellen Schmerztherapie. Neueren In-vitro-Studien zufolge ist jedoch die Applikation von Kontrastmittel weitgehend unbedenklich, während die von Lokalanästhetika wie Bupivacain eine gesunde Bandscheibe schädigen kann [10].…”

Section: Stellenwert Der Ct-diskografie Bei Unklarer Radikulopathieunclassified

Stellenwert der CT-Diskografie bei unklarer Radikulopathie

et al. 2011

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A clinically evident radiculopathy without correlation in the imaging studies represents a serious problem regarding the indication, planning and execution of an operative procedure for its treatment. Both the diagnosis and treatment of such cases are deemed to be difficult without clear morphological correlation. Moreover, the surgeon lacks an important basis for the adequate planning and above all the justification of surgical treatment. Although discography with post-discographic computer tomography (CT discography) is still controversially discussed as an invasive diagnostic measure, the literature shows that this method is not only useful but also indispensable in certain cases. Based on these findings and our own empirical data, we recommend CT discography to be considered for imaging in patients suffering from lumbar radiculopathy with equivocal or insufficient MRI findings. The technique allows an accurate diagnosis and precise planning of a targeted surgical intervention such as endoscopic sequestrotomy or decompression.

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Bupivacaine—the deadly friend of intervertebral disc cells?

Cited by 36 publications

References 22 publications

Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1β treated human intervertebral disc cells

Stellenwert der CT-Diskografie bei unklarer Radikulopathie

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