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.
IMPLICATIONS: 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.