Intrathecal administration of morphine, but not small dose, induced spastic paraparesis after a noninjurious interval of aortic occlusion in rats.
We sought to investigate the dose-response relationship for the effect of intrathecal morphine on the transient spastic paraparesis after short-lasting spinal ischemia in rats. Spinal ischemia was induced by aortic occlusion for 6 min with a balloon catheter in rats previously implanted with an intrathecal catheter for drug delivery. After ischemia, the animals were allowed to recover, and 3, 10, or 30 microg of morphine or saline was injected intrathecally at 30 min after reperfusion. In a separate group, the quantal bioassay for the effect of intrathecal morphine on neurological function after ischemia was performed to calculate 50% effective dose values for inducing paraparesis at 2 h of reperfusion. Subsequently, histopathology of the spinal cord was assessed at 48 h of reperfusion. Intrathecal injection of 30 or 10 micro g of morphine, but 3 micro g of neither morphine nor saline, caused a progressive development of hindlimb spasticity. The 50% effective dose values for inducing paraparesis were 16.1 +/- 1.5 microg in assessing behavioral analysis at 2 h after intrathecal morphine. Histopathological analysis of spinal cords in the 30- microg group revealed the presence of dark-staining alpha-motoneurons in lumbosacral segments. We conclude that spinal administration of a large dose of morphine after transient aortic occlusion may be associated with a potential risk of paraparesis and the corresponding development of neurological dysfunction. Careful attention should be paid when intrathecal morphine is used for pain control after thoracoabdominal aortic aneurysm repair.


CONCLUSIONS
Spinal administration of large-dose morphine after transient aortic occlusion may be associated with a potential risk of irreversible spinal neuronal degeneration and the corresponding development of neurological dysfunction.
Cousins
Michael J
MJ
Department of Anesthesiology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Kakinohana
Manabu
M
Fuchigami
Tatsuya
T
Nakamura
Seiya
S
Sasara
Takeshi
T
Kawabata
Tetsuya
T
Sugahara
Kazuhiro
K
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009046:Motor Neurons / Q000502:physiology; D020336:Paraparesis, Spastic / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000473:pathology / Q000503:physiopathology
D000701:Analgesics, Opioid; D009020:Morphine