Long-term effects of bupivacaine on cartilage in a rabbit shoulder model

Am J Sports Med. 2009 Jan;37(1):72-7. doi: 10.1177/0363546508323748. Epub 2008 Oct 2.


Background: Previous investigations have reported on the chondrotoxicity of bupivacaine in short-term in vivo and in vitro models. This study was designed to provide additional information on the long-term effects of bupivacaine infusion on articular cartilage in an established rabbit shoulder model.

Hypothesis: Infusion of bupivacaine into the rabbit shoulder will have long-term deleterious effects on articular cartilage.

Study design: Controlled laboratory study.

Methods: Thirty-six rabbits were randomized into 3 groups and were infused over 48 hours with saline (S), bupivacaine alone (B), or bupivacaine with epinephrine (B+E) into the glenohumeral joint. Animals were sacrificed after 3 months, and tissue samples were analyzed with live/dead cell assay, proteoglycan (PG) synthesis and content assays, and conventional histological evaluation.

Results: No macroscopic or radiographic changes were detected in the infused shoulders. Sulfate uptake of infused shoulders relative to controls was elevated to 112% +/-39% (S), 166% +/-67% (B), and 210% +/-127% (B+E). Statistical analysis of PG content demonstrated significantly increased levels in bupivacaine groups compared with saline. There were no significant differences among groups in cell count, percentage of living cells, or histological grade.

Conclusions: No permanent impairment of cartilage function was detected 3 months after intra-articular infusion of bupivacaine. Cartilage metabolism was increased, indicating a possible reparative response. This suggests that, at least in the model used, articular cartilage has the ability to recover from the chondrotoxic effects of bupivacaine infusion. Before extrapolating these results to human cartilage, other factors including underlying cartilage injury or disease, decreased chondrocyte density, and increased bupivacaine dosing need to be taken into account. Clinical Relevance Bupivacaine toxicity has recently been implicated in the development of chondrolysis after arthroscopic shoulder procedures, but these findings suggest that additional noxious stimuli might be required before permanent damage ensues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / pharmacology*
  • Animals
  • Bupivacaine / administration & dosage
  • Bupivacaine / pharmacology*
  • Cartilage, Articular / drug effects*
  • Outcome Assessment, Health Care
  • Pain / drug therapy
  • Rabbits
  • Random Allocation
  • Shoulder Joint / drug effects*


  • Anesthetics, Local
  • Bupivacaine