The effect of local anaesthetics on synoviocytes: a possible indirect mechanism of chondrolysis

Knee Surg Sports Traumatol Arthrosc. 2013 Jun;21(6):1468-74. doi: 10.1007/s00167-012-2104-5. Epub 2012 Jun 21.

Abstract

Purpose: While the effect of local anaesthetics on chondrocyte viability is widely documented, the effect of these medications on synoviocytes is largely unknown. The purpose of this study was to understand the effect of 0.5 % bupivacaine and 0.5 % bupivacaine with epinephrine on synoviocyte viability, cytokine and growth factor release, and breakdown product formation.

Methods: Rabbit fibroblast-like synoviocyte (Type B) cultures were perfused with 0.5 % bupivacaine or 0.5 % bupivacaine with epinephrine (1:200,000) for 24 h. Cell viability was evaluated using a two-colour fluorescence assay. The supernatant was analysed using multiplex inflammatory and matrix metalloproteinase assays.

Results: Synoviocytes treated for 24 h with 0.5 % bupivacaine with epinephrine demonstrated a significant decrease in viability (31.3 ± 19.4 % cell death) when compared with synoviocytes cultured in control media (3.8 ± 1.3 % cell death, p = 0.000) and those cultured in 0.5 % bupivacaine alone (12.6 ± 11.1 % cell death, p = 0.003). No significant decrease in cell viability was observed in synoviocytes treated with 0.5 % bupivacaine compared to those in control media (12.6 ± 11.1 % vs 3.8 ± 1.3 % cell death, p = 0.194). Significantly greater amounts of MMP-1 (47.0 ± 9.2 pg/ml) and MMP-3 (250.0 ± 68.8 pg/ml) were observed in 0.5 % bupivacaine cultures compared with controls (14.3 ± 14.3, p = 0.023 and 72.0 ± 84.9, p = 0.045, respectively).

Conclusions: 0.5 % bupivacaine with epinephrine caused a significant increase in cell death of the synoviocytes, while 0.5 % bupivacaine alone produced cell injury and a significant release of matrix metalloproteinases, which may also lead to indirect injury of the surrounding chondrocytes. These results may help explain the onset of chondrolysis observed in patients who have been treated with intra-articular local anaesthetics.

MeSH terms

  • Anesthetics, Local / pharmacology*
  • Animals
  • Bupivacaine / pharmacology*
  • Cell Culture Techniques
  • Cell Survival
  • Cytokines / biosynthesis
  • Drug Combinations
  • Epinephrine / pharmacology
  • Injections, Intra-Articular
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Rabbits
  • Synovial Membrane / cytology*
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism
  • Vasoconstrictor Agents / pharmacology

Substances

  • Anesthetics, Local
  • Cytokines
  • Drug Combinations
  • Intercellular Signaling Peptides and Proteins
  • Vasoconstrictor Agents
  • Bupivacaine
  • Epinephrine