title: Neuraxial morphine may trigger transient motor dysfunction after a noninjurious interval of spinal cord ischemia: a clinical and experimental study.
abstract: BACKGROUND
  A patient underwent repair of a thoracoabdominal aortic aneurysm. Epidural morphine, 4 mg, was given for pain relief. After anesthesia, the patient displayed lower extremity paraparesis. This effect was reversed by naloxone. The authors sought to confirm these observations using a rat spinal ischemia model to define the effects of intrathecal morphine administered at various times after reflow on behavior and spinal histopathology.
  
  
  METHODS
  Spinal cord ischemia was induced for 6 min using an intraaortic balloon. Morphine or saline, 30 microg, was injected intrathecally at 0.5, 2, or 24 h after reflow. In a separate group, spinal cord temperature was decreased to 27 degrees C before ischemia. After ischemia, recovery of motor function was assessed periodically using the motor deficit index (0 = complete recovery; 6 = complete paraplegia).
  
  
  RESULTS
  After ischemia, all rats showed near-complete recovery of function by 4-6 h. Intrathecal injection of morphine at 0.5 or 2 h of reflow (but not at 24 h) but not saline caused a development of hind limb dysfunction and lasted for 4.5 h (motor deficit index score = 4-6). This effect was reversed by intrathecal naloxone (30 microg). Intrathecal morphine administered after hypothermic ischemia was without effect. Histopathological analysis in animals that received intrathecal morphine at 0.5 or 2 h after ischemia (but not at 24 h) revealed dark-staining alpha motoneurons and interneurons. Intrathecal saline or spinal hypothermia plus morphine was without effect.
  
  
  CONCLUSIONS
  These data indicate that during the immediate reflow following a noninjurious interval of spinal ischemia, intrathecal morphine potentiates motor dysfunction. Reversal by naloxone suggests that this effect results from an opioid receptor-mediated potentiation of a transient block of inhibitory neurons initiated by spinal ischemia.
authors.affiliation: Department of Anesthesiology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kakinohana
authors.forename: Martin
authors.initials: M
authors.lastname: Marsala
authors.forename: Christopher
authors.initials: C
authors.lastname: Carter
authors.forename: J Kenneth
authors.initials: JK
authors.lastname: Davison
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000503:physiopathology; D003250:Constriction; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000150:complications* / Q000473:pathology; D016707:Tissue Fixation; D014656:Vascular Surgical Procedures
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine