title: Opioids as an alternative to amide-type local anaesthetics for intra-articular application.
abstract: OBJECTIVE
  Recently, the safety profile of local anaesthetics in intra-articular use became into focus of investigation. Opioid drugs have a different mode of action and may be a safe and potent alternative for intra-articular application. The purpose of this in vitro study is to provide evidence for significant chondrotoxicity of amide-type local anaesthetics even after short-term application on human chondrocytes and to demonstrate the absence of such negative effects for opioids [morphine, morphine-6-glucuronide (M6G)].
  
  
  METHODS
  Visually intact cartilage explants of human, mainly osteoarthritic joints (n = 9), were harvested and cultivated in monolayer for expansion and transferred into alginate bead. The beads were incubated for increasing incubation times (15 min, 1 and 4 h) in decreasing concentrations (full, ½, ¼ for 15 min) of bupivacaine, ropivacaine, morphine, M6G or saline control. Adenosine triphosphate content of 798 beads was measured 3 days post-incubation to assess cell viability.
  
  
  RESULTS
  A clear ranking of cytotoxic potency: bupivacaine > ropivacaine > morphine = M6G = saline was observed. Results reveal a dose- and time-dependent manner of cytotoxic effects on human chondrocytes for bupivacaine and ropivacaine but not for opioids. Cell viability after exposure to morphine and M6G was comparable to exposure to saline.
  
  
  CONCLUSIONS
  The results confirm dose- and time-dependent cytotoxic effects on human chondrocytes for amide-type local anaesthetics. This study confirms the safety of morphine and M6G in terms of an absence of cytotoxic effects after intra-articular application, making them safe potential alternatives in clinical practice.
authors.affiliation: Department of Orthopedics, University Hospital, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Ickert
authors.forename: Monika
authors.initials: M
authors.lastname: Herten
authors.forename: Melanie
authors.initials: M
authors.lastname: Vogl
authors.forename: Christoph
authors.initials: C
authors.lastname: Ziskoven
authors.forename: Christoph
authors.initials: C
authors.lastname: Zilkens
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Krauspe
authors.forename: Jörn
authors.initials: J
authors.lastname: Kircher
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002045:Bupivacaine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects*; D006801:Humans; D007270:Injections, Intra-Articular; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009022:Morphine Derivatives; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; D000077212:Ropivacaine; D002045:Bupivacaine