The effect of local anaesthetics on synoviocytes: a possible indirect mechanism of chondrolysis.
OBJECTIVE
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.
Department of Orthopaedic Surgery, Stanford University, Redwood City, CA 94063-6342, USA.
Hillary J
HJ
Braun
Benjamin T
BT
Busfield
Hyeon Joo
HJ
Kim
Gaetano J
GJ
Scuderi
Jason L
JL
Dragoo
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D004338:Drug Combinations; D004837:Epinephrine / Q000494:pharmacology; D007270:Injections, Intra-Articular; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000779:Anesthetics, Local; D016207:Cytokines; D004338:Drug Combinations; D036341:Intercellular Signaling Peptides and Proteins; D014662:Vasoconstrictor Agents; D002045:Bupivacaine; D004837:Epinephrine