Biologia, Bratislava 54/Suppl. 6: 51-60, 1999.

ISSN 0006-3088 (Biologia). ISSN 1335-6399 (Biologia. Section Cellular and Molecular Biology).


Full paper

Repetitive intrathecal administration of morphine induces irreversible paraplegia after non-injurious interval of spinal cord ischemia in the rat.


Tatsuya Fuchigami1*, Yutaka Taira1, Manabu Kakinohana1, Osamu Kakinohana1, Martin Marsala2 Hiroshi Iha1 & Yoshiaki Okuda1

1 Department of Anesthesiology, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan; tel.: ++81 98 895 3331, fax: ++81 98 8952560, e-mail:

2 Department of Anesthesiology, University of California at San Diego, California, USA

* corresponding author

Received: June 30, 1999 / Accepted: October 5, 1999



Previous clinical studies have shown that a single intrathecal injection of morphine triggers the development of spasticity, if administered during early period of reflow after transient short-lasting aortic cross clamp. This effect is completely reversed by Naloxone. In the present study, using a rat aortic occlusion model we characterize the effect of single and repetitive intrathecal (IT) injections of morphine, if injected, after non-injurious interval of spinal ischemia on i) neurological outcome and ii) spinal histopathology. Rats previously implanted with intrathecal catheter for drug delivery were exposed to 6 min of spinal ischemia. At 1 hr and/or 5 hrs after reflow rats received 30 mg of intrathecal morphine. In control animals saline was injected intrathecally. After injections rats were allowed to recover and were periodically assessed for the recovery of motor functions for 3 days. After 3 days rats were perfusion fixed and spinal cord analyzed for the presence of histopathological changes. In control animals IT injections of saline had no apparent effect on the recovery of motor function and all animals showed near complete recovery at 48 hrs after reflow. A single IT injection of morphine at 1 hr after ischemia resulted in a development of spasticity which disappeared between 8-24 hrs after injection. In some animals a second IT injection of morphine resulted in permanent paraplegia and this effect was only partially ameliorated by Naloxone treatment. In these animals histopathological analysis of lumbosacral spinal cord revealed the presence of numerous dark staining neurons or small fragments of their disintegrated bodies. These data suggest that spinal administration of high doses of opioids, when injected after transient aortic occlusion, may be associated with potential risk of irreversible spinal neuronal degeneration and corresponding development of neurological dysfunction.


Key words: spinal ischemia, paraplegia, intrathecal, morphine, Naloxone.