Cytotoxicity of local anesthetics to rats' articular cartilage: an experimental study

The aim of this study was to evaluate the effects of both in vivo and in vitro bupivacaine, levobupivacaine and tramadol on articular cartilage and chondrocytes in experimental rat models.

Thirty mature Sprague Dawley rats weighing 230-300 g were randomized into 3 groups. Bupivacaine (Group 1), levobupivacaine (Group 2) and tramadol (Group 3) were injected into the right knee joints and a physiological 0.9% saline into the left. From each group, 5 rats were executed 48 hours following drug administration after 5 and 10 days. The specimens were fixed, decalcified and stained with hematoxylin & eosin and toluidine blue. All samples were histopathologically evaluated according to the recommendation of ICRS' osteoarthritis and cartilage histopathology grading and staging system. Articular cartilage cells of the rats were cultured and seeded into cell culture flasks. Cartilage cell seeded samples (104 cells/ml) were incubated in three different anesthetic agents (0.5%); bupivacaine, levobupivacaine, and tramadol, respectively. CellTiter 96(®) Non-Radioactive Cell Proliferation (MTS) assay was used to determine the cell density on the samples.

Statistically significant higher OARSI grades and OA stage and scores were detected when comparing the group injected with levobupivacaine and executed after 10 days with the levobupivacaine injected group killed after 48 hours (p<0.01 [p=0.008]). Although, statistical analysis could not be done due to insufficient number of samples in the in vitro part of the experiment, it can be concluded that tramadol is cytotoxic to rat chondrocyte in vitro after 30 min of exposure. Additionally, cell numbers in both the bupivacaine and levobupivacaine treated wells showed decrease throughout 15, 30 and 60 minute exposures.

Although chondrotoxicity of bupivacaine was less harmful than levobupivacaine and tramadol, these findings suggest that local anesthetics may negatively affect articular cartilage and chondrocytes.