Skip to main content
SpringerLink
Log in

In vivo effects of bupivacaine and gadobutrol on the intervertebral disc following discoblock and discography: a histological analysis

  • Interventional
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

The aim of the present study was to histologically compare chondrotoxicity in surgically harvested intervertebral discs (IVDs) of patients following discoblock, discography, or no preoperative intervention.

Methods

Thirty patients (IVD degeneration Modic ≥ 2°, Pfirrmann 3° or 4°) at L4/5 or L5/S1 who were planned for anterior lumbar interbody fusion were randomly assigned to three groups (open MRI: group DG - discography with gadobutrol; group DB - discoblock with bupivacaine at 4 weeks prior to surgery; group C - no intervention). The intervertebral discs were histologically evaluated and compared using ANOVA and Bonferroni tests for cell count, apoptosis, and proliferation.

Results

A reduced cell count (groups DG vs. DB vs. C: 14.9 ± 7.1, 9.2 ± 3.8, and 16.6 ± 5.2 cells/mm2, respectively; p ANOVA = 0.016), increased apoptosis (groups DG vs. DB vs. C: 34.9 ± 10.2, 47.4 ± 16.3, 32.6 ± 12.2 %, respectively; p ANOVA = 0.039) and increased cell proliferation (post hoc pDB vs. DG or C p < 0.001; for 3-7 cell monoclonal cell nests: groups DG vs. DB vs. C: 2.4 ± 1, 3.9 ± 1, 2.2 ± 1.1, respectively; p intervention x nest size = 0.006) were found in the IVDs of patients in group DB.

Conclusions

This in vivo study suggests that chondrotoxic effects occur in IVD cells after the intradiscal injection of bupivacaine but not after gadobutrol administration.

Key Points

• Local bupivacaine administration to intervertebral discs leads to cell toxicity and proliferation.

• Gadobutrol demonstrated no significant effect on cell count, apoptosis, or cell proliferation.

• In vivo cytotoxicity was demonstrated histologically in humans for the first time.

• Addition/administration of bupivacaine during discographies must be judged critically.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

IVD:

intervertebral disc

GBCA:

gadolinium-based contrast agent

ALIF:

anterior lumbar intervertebral fusion

ANOVA:

analysis of variance

References

  1. Manchikanti L, Benyamin RM, Singh V, Falco FJ, Hameed H, Derby R et al (2013) An update of the systematic appraisal of the accuracy and utility of lumbar discography in chronic low back pain. Pain Phys 16:SE55–SE95

    Google Scholar 

  2. Cohen SP, Larkin TM, Barna SA, Palmer WE, Hecht AC, Stojanovic MP (2005) Lumbar discography: a comprehensive review of outcome studies, diagnostic accuracy, and principles. Reg Anesth Pain Med 30:163–183

    PubMed  Google Scholar 

  3. Ohtori S, Kinoshita T, Yamashita M, Inoue G, Yamauchi K, Koshi T et al (2009) Results of surgery for discogenic low back pain: a randomized study using discography versus discoblock for diagnosis. Spine (Phila Pa 1976) 34:1345–1348

    Article  Google Scholar 

  4. Derby R, Lee JE, Lee SH (2010) [Epub ahead of print]) analgesic discography: effect of adding a local anesthetic to routine lumbar provocation discography. Pain Med 11:1335–1342

    Article  PubMed  Google Scholar 

  5. Derby R, Aprill CN, Lee JE, DePalma MJ, Baker RM (2012) Comparison of four different analgesic discogram protocols comparing the incidence of reported pain relief following local anesthetic injection into concordantly painful lumbar intervertebral discs. Pain Med 13:1547–1553

    Article  PubMed  Google Scholar 

  6. Bartynski WS, Rothfus WE (2007) Pain improvement after intradiskal lidocaine administration in provocation lumbar diskography: association with diskographic contrast leakage. AJNR Am J Neuroradiol 28:1259–1265

    Article  CAS  PubMed  Google Scholar 

  7. Putzier M, Streitparth F, Hartwig T, Perka CF, Hoff EK, Strube P (2013) Can discoblock replace discography for identifying painful degenerated discs? Eur J Radiol 82:1463–1470

    Article  PubMed  Google Scholar 

  8. Alamin TF, Kim MJ, Agarwal V (2011) Provocative lumbar discography versus functional anesthetic discography: a comparison of the results of two different diagnostic techniques in 52 patients with chronic low back pain. Spine J 11:756–765

    Article  PubMed  Google Scholar 

  9. Carragee EJ, Don AS, Hurwitz EL, Cuellar JM, Carrino J, Herzog R (2009) 2009 ISSLS prize winner: does discography cause accelerated progression of degeneration changes in the lumbar disc: a ten-year matched cohort study. Spine (Phila Pa 1976) 34:2338–2345

    Article  Google Scholar 

  10. Breu A, Rosenmeier K, Kujat R, Angele P, Zink W (2013) The cytotoxicity of bupivacaine, ropivacaine, and mepivacaine on human chondrocytes and cartilage. Anesth Analg 117:514–522

    Article  CAS  PubMed  Google Scholar 

  11. Cai XY, Xiong LM, Yang SH, Shao ZW, Xie M, Gao F et al (2014) Comparison of toxicity effects of ropivacaine, bupivacaine, and lidocaine on rabbit intervertebral disc cells in vitro. Spine J 14:483–490

    Article  PubMed  Google Scholar 

  12. Chee AV, Ren J, Lenart BA, Chen EY, Zhang Y, An HS (2014) Cytotoxicity of local anesthetics and nonionic contrast agents on bovine intervertebral disc cells cultured in a three-dimensional culture system. Spine J 14:491–498

    Article  PubMed  Google Scholar 

  13. Eder C, Pinsger A, Schildboeck S, Falkner E, Becker P, Ogon M (2013) Influence of intradiscal medication on nucleus pulposus cells. Spine J 13:1556–1562

    Article  PubMed  Google Scholar 

  14. Gruber HE, Rhyne AL 3rd, Hansen KJ, Phillips RC, Hoelscher GL, Ingram JA et al (2012) Deleterious effects of discography radiocontrast solution on human annulus cell in vitro: changes in cell viability, proliferation, and apoptosis in exposed cells. Spine J 12:329–335

    Article  PubMed  Google Scholar 

  15. Iwasaki K, Sudo H, Yamada K, Higashi H, Ohnishi T, Tsujimoto T et al (2014) Effects of single injection of local anesthetic agents on intervertebral disc degeneration: ex vivo and long-term in vivo experimental study. PLoS One 9, e109851

    Article  PubMed  PubMed Central  Google Scholar 

  16. Iwasaki K, Sudo H, Yamada K, Ito M, Iwasaki N (2014) 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. PLoS One 9, e92442

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lee H, Sowa G, Vo N, Vadala G, O'Connell S, Studer R et al (2010) Effect of bupivacaine on intervertebral disc cell viability. Spine J 10:159–166

    Article  PubMed  Google Scholar 

  18. Wang D, Vo NV, Sowa GA, Hartman RA, Ngo K, Choe SR et al (2011) Bupivacaine decreases cell viability and matrix protein synthesis in an intervertebral disc organ model system. Spine J 11:139–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Quero L, Klawitter M, Nerlich AG, Leonardi M, Boos N, Wuertz K (2011) Bupivacaine--the deadly friend of intervertebral disc cells? Spine J 11:46–53

    Article  PubMed  Google Scholar 

  20. Streitparth F, Hartwig T, Schnackenburg B, Strube P, Putzier M, Chopra S et al (2011) MR-guided discography using an open 1 Tesla MRI system. Eur Radiol 21:1043–1049

    Article  PubMed  Google Scholar 

  21. Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR (1988) Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology 166:193–199

    Article  CAS  PubMed  Google Scholar 

  22. Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N (2001) Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 26:1873–1878

    Article  CAS  Google Scholar 

  23. Gerbershagen HU, Lindena G, Korb J, Kramer S (2002) Health-related quality of life in patients with chronic pain. Schmerz 16:271–284

    Article  CAS  PubMed  Google Scholar 

  24. Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG (2002) Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine (Phila Pa 1976) 27:2631–2644

    Article  Google Scholar 

  25. Wack C, Steger-Hartmann T, Mylecraine L, Hofmeister R (2012) Toxicological safety evaluation of gadobutrol. Invest Radiol 47:611–623

    Article  CAS  PubMed  Google Scholar 

  26. Cho S, Lee Y, Lee S, Choi YJ, Chung HW (2014) Enhanced cytotoxic and genotoxic effects of gadolinium following ELF-EMF irradiation in human lymphocytes. Drug Chem Toxicol 37:440–447

    Article  CAS  PubMed  Google Scholar 

  27. Greisberg JK, Wolf JM, Wyman J, Zou L, Terek RM (2001) Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes. J Orthop Res 19:797–801

    Article  CAS  PubMed  Google Scholar 

  28. Behra-Miellet J, Gressier B, Brunet C, Dine T, Luyckx M, Cazin M et al (1996) Free gadolinium and gadodiamide, a gadolinium chelate used in magnetic resonance imaging: evaluation of their in vitro effects on human neutrophil viability. Methods Find Exp Clin Pharmacol 18:437–442

    CAS  PubMed  Google Scholar 

  29. Moon JH, Kuh SU, Park HS, Kim KH, Park JY, Chin DK et al (2012) Triamcinolone decreases bupivacaine toxicity to intervertebral disc cell in vitro. Spine J 12:665–673

    Article  PubMed  Google Scholar 

  30. Liebscher T, Haefeli M, Wuertz K, Nerlich AG, Boos N (2011) Age-related variation in cell density of human lumbar intervertebral disc. Spine (Phila Pa 1976) 36:153–159

    Article  Google Scholar 

Download references

Acknowledgments

The scientific guarantor of this publication is Michael Putzier, Centrum für Muskuloskeletale Chirurgie, Charité – Universitätsmedizin Berlin. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective, randomised controlled trial, performed at one institution.

Author information

Authors and Affiliations

  1. Klinik für Orthopädie, Friedrich-Schiller-Universität Jena, Campus Waldkrankenhaus “Rudolf Elle” Eisenberg, Klosterlausnitzer Strasse 81, 07607, Eisenberg, Germany

    Patrick Strube

  2. Institut für Pathologie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Berit M. Pfitzner

  3. Klinik für Radiologie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Florian Streitparth

  4. Klinik für Orthopädie, Centrum für Muskuloskeletale Chirurgie, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Tony Hartwig & Michael Putzier

Authors
  1. Patrick Strube
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Berit M. Pfitzner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Florian Streitparth
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tony Hartwig
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Putzier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick Strube.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Strube, P., Pfitzner, B.M., Streitparth, F. et al. In vivo effects of bupivacaine and gadobutrol on the intervertebral disc following discoblock and discography: a histological analysis. Eur Radiol 27, 149–156 (2017). https://doi.org/10.1007/s00330-016-4358-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-016-4358-7

Keywords

Search

Navigation