The Knee, Volume 27, Issue 6, 2020, Pages 1746-1752, ISSN 0968-0160.

Acetaminophen, bupivacaine, Duramorph, and Toradol: A comparison of chondrocyte viability and gene expression changes in osteoarthritic human chondrocytes

Christopher Cooke, Jeffrey Osborne, Nancy Jackson, Patrick Keating, Jeff Flynn, David Markel, Chaoyang Chen, Stephen Lemos.


A multitude of chemical agents are currently used intra-articularly to decrease pain after orthopaedic procedures including total knee arthroplasty. However, the possible deleterious effects of these injectable chemicals on chondrocyte viability have not been weighed against their potential benefits. Using a human osteoarthritic chondrocyte model, the purpose of this study was to assess the potential for cartilage damage caused by bupivacaine, Toradol, Duramorph, and acetaminophen from surgical local anesthesia.


Human distal femur and proximal tibia cross sections were obtained during total knee arthroplasty and divided into control group and experimental groups treated by bupivacaine, Toradol, Duramorph, and acetaminophen respectively. Chondrocytes obtained from enzymatically digested cartilage were cultured using a 3D alginate bead culture method to ensure lower rates of dedifferentiation. Chondrocyte bead cultures were exposed to the study chemicals. The gene expression and chondrocyte viability were measured by RT-PCR and flow cytometry, respectively.


Compared with untreated group bupivacaine treatment led to the greatest cellular apoptosis with 30.5 ± 11% dead cells ( P = 0.000). Duramorph and acetaminophen did not result in a significant increase in cell death. Bupivacaine treatment led to an increase in Caspase 3 gene expression ( P = 0.000) as well as the acetaminophen treatment ( P = 0.001) when compared to control.


Our data demonstrated that Duramorph and Toradol were not cytotoxic to human chondrocytes and may be better alternatives to the frequently used and more cytotoxic bupivacaine. Acetaminophen did not result in increased cell death; however, it did show increased caspase 3 gene expression and caution should be considered.

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