Journal of Dental Anesthesia and Pain Medicine

The Korean Dental Society of Anesthsiology (대한치과마취과학회)
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Narrative review: the evidence for neurotoxicity of dental local anesthetics

  • Aps, Johan (Division of Oral Diagnostics and Surgical Sciences, University of Western Australia) ;
  • Badr, Nelly (University of Washington)
  • Received : 2019.12.18
  • Accepted : 2020.03.29
  • Published : 2020.04.29
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Abstract

Dental local anesthesia is performed daily on a global scale. Adverse effects are rare, but the topic of neurotoxicity of local anesthetics deserves to be explored, as publications can be controversial and confusing. Therefore, a need was felt to address and question the evidence for potential neurotoxicity of dental local anesthetics. This review aimed to assess the studies published on the neurotoxicity of dental local anesthetics. A PubmedⓇ search was conducted between January 2019 and August 2019. This revealed 2802 hits on the topic of neurotoxicity or cytotoxicity of the following anesthetics: lidocaine, prilocaine, mepivacaine, articaine, ropivacaine, and bupivacaine. Only 23 papers were deemed eligible for this review: 17 in vitro studies, 3 reviews and 3 audits of national inquiries. The heterogeneous literature on this topic showed that all dental local anesthetics are potentially neurotoxic in a concentration and/or exposure time fashion. There seems no consensus about what cell lines are to be used to investigate the neurotoxicity of local anesthetics, which makes the comparison between studies difficult and ambiguous. However, the bottom line is that all dental local anesthetics have a neurotoxic potential, but that there is no unanimity in the publications about which local anesthetic is the least or the most neurotoxic.

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References

  1. Garisto GA, Gaffen AS, Lawrence HP, Tenenbaum HC, Haas DA. Occurrence of paresthesia after dental local anesthetic administration in the United States. J Am Dent Assoc 2010; 141: 836-44. https://doi.org/10.14219/jada.archive.2010.0281
  2. Piccinni C, Gissi DB, Gabusi A, Montebugnoli L, Poluzzi E. Paraesthesia after local anaesthetics: an analysis of reports to the FDA Adverse Event Reporting System. Basic Clin Pharmacol Toxicol 2015; 117: 52-6. https://doi.org/10.1111/bcpt.12357
  3. Haas DA, Lennon D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J Can Dent Assoc 1995; 61: 319-20.
  4. Pogrel MA. Permanent nerve damage from inferior alveolar nerve blocks: a current update. J Calif Dent Assoc 2012; 40: 795-7.
  5. Dower JS Jr. A review of paresthesia in association with administration of local anesthesia. Dent Today 2003; 22: 64-9.
  6. Hillerup S, Jensen R. Nerve injury caused by mandibular block analgesia. Int J Oral Maxillofac Surg 2006; 35: 437-43. https://doi.org/10.1016/j.ijom.2005.10.004
  7. Malamed SF. Local anesthetics: dentistry's most important drugs, clinical update 2006. J Calif Dent Assoc 2006; 34: 971-6.
  8. Peltier B, Dower JS Jr. The ethics of adopting a new drug: articaine as an example. J Am Coll Dent 2006; 73: 11-20.
  9. Haas DA. Localized complications from local anesthesia. J Calif Dent Assoc 1998; 26: 677-82.
  10. Haas DA. Articaine and paresthesia: epidemiological studies. J Am Coll Dent 2006; 73: 5-10.
  11. Oliveira AC, Rodriguez IA, Garzon I, Martin-Piedra MA, Alfonso-Rodriguez CA, Garcia JM, et al. An early and late cytotoxicity evaluation of lidocaine on human oral mucosa fibroblasts. Exp Biol Med 2014; 239: 71-82. https://doi.org/10.1177/1535370213503274
  12. Cela O, Piccoli C, Scrima R, Quarato G, Marolla A, Cinnella G, et al. Bupivacaine uncouples the mitochondrial oxidative phosphorylation, inhibits respiratory chain complexes I and III and enhances ROS production: results of a study in cell cultures. Mitochondrion 2010; 10: 487-96. https://doi.org/10.1016/j.mito.2010.05.005
  13. Haasters F, Polzer H, Prall WC, Saller MM, Kohler J, Grote S, et al. Bupivacaine, ropivacaine, and morphine: comparison of toxicity on human hamstring-derived stem/progenitor cells. Knee Surg Sports Traumatol Arthosc 2011; 19: 2138-44. https://doi.org/10.1007/s00167-011-1564-3
  14. Zhang AZ, Ficklscherer A, Gulecyuz MF, Paulus AC, Niethammer TR, Jansson V, et al. Cell toxicity in fibroblasts, tenocytes, and human mesenchymal stem cells - a comparison of necrosis and apoptosis-inducing ability in ropivacaine, bupivacaine and triamcinolone. Arthroscopy 2017; 33: 840-8. https://doi.org/10.1016/j.arthro.2016.10.026
  15. Kang DK, Zhao LY, Wang HL. Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines. Braz J Anesthesiol 2016; 66: 594-602. https://doi.org/10.1016/j.bjan.2016.08.002
  16. Sung CM, Hah YS, Kim JS, Nam JB, Kim RJ, Lee SJ, et al. Cytotoxic effects of ropivacaine, bupivacaine and lidocaine on rotator cuff tenofibroblasts. Am J Sports Med 2014; 42: 2888-96. https://doi.org/10.1177/0363546514550991
  17. Kobayashi K, Ohno S, Uchida S, Amano O, Sakagami H, Nagasaka H. Cytotoxicity and type of cell death induced by local anesthetics in human oral normal and tumor cells. Anticancer Res 2012; 32: 2925-33.
  18. Breu A, Eckl S, Zink W, Kujat R, Angele P. Cytotoxicity of local anesthetics on human mesenchymal stem cells in vitro. Arthroscopy 2013; 29: 1676-84. https://doi.org/10.1016/j.arthro.2013.06.018
  19. Rahnama R, Wang M, Dang AC, Kim HT, Kuo AC. Cytotoxicity of local anesthetics in human mesenchymal stem cells. J Bone Joint Surg Am 2013; 95: 132-7. https://doi.org/10.2106/JBJS.K.01291
  20. Honda H, Gotoh M, Kanazawa T, Nakamura H, Ohta K, Nakamura K, et al. Effects of lidocaine on torn rotator cuff tendons. J Orthop Res 2016; 34: 1620-7. https://doi.org/10.1002/jor.23153
  21. Werdehausen R, Braun S, Fazeli S, Hermanns H, Hollmann MW, Bauer I, et al. Lipophilicity but not stereospecificity is a major determinant of local anesthetic- induced cytotoxicity in human T-lymphoma cells. Eur J Anaesthesiol 2012; 29: 35-41.
  22. Breu A, Scheidhammer I, Kujat R, Graf B, Angele P. Local anesthetic cytotoxicity on human mesenchymal stem cells during chondrogenic differentiation. Knee Surg Sports Traumatol Arthrosc 2015; 23: 937-45. https://doi.org/10.1007/s00167-014-3312-y
  23. Breu A, Rosenmeier K, Kujat R, Angele P, Zink W. The cytotoxicity of bupivacaine, ropivacaine and mepivacaine on human chondrocytes and cartilage. Anesth Analg 2013; 117: 514-22. https://doi.org/10.1213/ANE.0b013e31829481ed
  24. Jacobs TF, Vansintjan PS, Roels N, Herregods SS, Verbruggen G, Herregods LL, et al. The effect of lidocaine on the viability of cultivated mature human cartilage cells: an in vitri study. Knee Surg Sports Arthroasc 2011; 19: 1206-13. https://doi.org/10.1007/s00167-011-1420-5
  25. Perez-Castro R, Patel S, Garavito-Aguilar ZV, Rosenberg A, Recio-Pinto E, Zhang J, et al. Cytotoxicity of local anesthetics in human neuronal cells. Anesth Analg 2009; 108: 997-1007. https://doi.org/10.1213/ane.0b013e31819385e1
  26. Malet A, Faure MO, Delatage N, Pereira B, Haas J, Lambert G. The comparative cytotoxic effects of different local anesthetics on human neuroblastoma cell line. Anesth Analg 2015; 120: 589-96. https://doi.org/10.1213/ANE.0000000000000562
  27. Albalawi F, Lim JC, DiRenzo KV, Hersch EV, Mitchell CH. Effects of lidocaine and articaine on neuronal survival and recovery. Anesth Prog 2018; 65: 82-8. https://doi.org/10.2344/anpr-65-02-02
  28. Kreuz PC, Steinwachs M, Angele P. Single-dose local anesthetics exhibit a type-, dose-, and time-dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature. Knee Surh Sports Arthrosc 2018; 26: 819-30. https://doi.org/10.1007/s00167-017-4470-5
  29. Hopman AJG, Baart JA, Brand HS. Articaine and neurotoxicity - a review. Br Dent J 2017; 223: 501-6. https://doi.org/10.1038/sj.bdj.2017.782
  30. Wu T, Smith J, Nie H, Wang Z, Erwin PJ, van Wijnen AJ, et al. Cytotoxicity of local anesthetics in mesenchymal stem cells. Am J Phys Med Rehabil 2018; 97: 50-5. https://doi.org/10.1097/PHM.0000000000000837
  31. Barrington MJ, Watts SA, Gledhill SR, Thomas RD, Said SA, Snyder GL, et al. Preliminary results of the Australasian regional anesthesia collaboration. A retrospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and other complications. Reg Anesth Pain Med 2009; 34: 534-41. https://doi.org/10.1097/AAP.0b013e3181ae72e8
  32. Badr N, Aps J. Efficacy of dental local anesthetics: a review. J Dent Anesth Pain Med 2018; 18: 319-32. https://doi.org/10.17245/jdapm.2018.18.6.319
  33. Hillerup S, Jensen RH, Ersboll BK. Trigeminal nerve injury associated with injection of local anesthetics: needle lesion or neurotoxicity? J Am Dent Assoc 2011; 142: 531-9. https://doi.org/10.14219/jada.archive.2011.0223
  34. Martin M, Nusstein J, Drum M, Reader A, Beck M. Anesthetic efficacy of 1.8 mL versus 3.6 mL of 4% articaine with 1:100,000 epinephrine as a primary buccal infiltration of the mandibular first molar. J Endod 2011; 37: 588-92. https://doi.org/10.1016/j.joen.2011.01.001
  35. Nydegger B, Nusstein J, Reader A, Drum M, Beck M. Anesthetic comparisons of 4% concentrations of articaine, lidocaine, and prilocaine as primary buccal infiltrations of the mandibular first molar: a prospective randomized, double-blind study. J Endod 2014; 40: 1912-6. https://doi.org/10.1016/j.joen.2014.08.001
  36. Kammerer PW, Schneider D, Palarie V, Schiegnitz E, Daublander M. Comparison of anesthetic efficacy of 2 and 4% articaine in inferior alveolar nerve block for tooth extraction - a double-blind randomized clinical trial. Clin Oral Investig 2017; 21: 397-403. https://doi.org/10.1007/s00784-016-1804-5
  37. Pogrel MA, Schmidt BL, Sambajon V, Jordan RC. Lingual nerve damage due to inferior alveolar nerve blocks: a possible explanation. J Am Dent Assoc 2003; 134: 195-9. https://doi.org/10.14219/jada.archive.2003.0133