The effect of bupivacaine and morphine in a coculture model of diarthrodial joints.
OBJECTIVE
To perform a controlled laboratory study to evaluate the effect of bupivacaine and morphine on chondrocytes and synovium in a coculture model of diarthrodial joints.


METHODS
A proven coculture model that allows for the assessment of cartilage and synovium exists. The model allows for simulation of the diarthrodial joint in both health and disease by using culture media with or without the addition of interleukin-1. Effects of the presence of bupivacaine and morphine were evaluated by measuring media concentration of glycosamino glycans (GAG), nitric oxide (NO), and prostaglandin E(2) (PGE(2)), and tissue concentration of GAG, water, and collagen. Cell viability was determined through the use of confocal microscopy on days 1 and 2.


RESULTS
Cell viability 2 days after exposure to 0.5% bupivacaine was significantly less in the presence of bupivacaine than in the other groups, nearing a 100% decrease in viability. There was little effect of bupivacaine on cartilage water content or the tissue concentration of GAG and collagen. Morphine and bupivacaine both inhibited the expected rise in NO and PGE(2) when interleukin-1 was added to the media.


CONCLUSIONS
Continuous 0.5% bupivacaine exposure has a clear detrimental effect on chondrocytes in this in vitro study. Both bupivacaine and morphine appear to have anti-inflammatory effects. Continuous morphine exposure does not cause gross chondrotoxicity in vitro and presents itself as a potential alternative intra-articular analgesic.


CONCLUSIONS
Intra-articular bupivacaine infusion is an effective analgesic strategy and is frequently used in both office and outpatient surgical settings. This study provides evidence that the continued usage of postoperative bupivacaine continuous infusion pumps may have a detrimental effect on chondrocytes. Morphine has been shown to be an effective intra-articular analgesic, and its anti-inflammatory role seen in this study makes it a potential alternative to bupivacaine.
Anz
Alan
A
Department of Orthopaedic Surgery, University of Missouri-Columbia, Columbia, Missouri 65212, USA. AnzA@health.missouri.edu
Smith
Matthew J
MJ
Stoker
Aaron
A
Linville
Cole
C
Markway
Heather
H
Branson
Keith
K
Cook
James L
JL
D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use; D000779:Anesthetics, Local / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D001834:Body Water / Q000378:metabolism; D002045:Bupivacaine / Q000009:adverse effects / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects; D004285:Dogs; D004359:Drug Therapy, Combination; D005065:Euthanasia; D007596:Joints / Q000187:drug effects / Q000503:physiopathology*; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*
D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D009020:Morphine; D002045:Bupivacaine