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CARDIOVASCULAR ANESTHESIA

The Activation of Spinal N-Methyl-d-Aspartate Receptors May Contribute to Degeneration of Spinal Motor Neurons Induced by Neuraxial Morphine After a Noninjurious Interval of Spinal Cord Ischemia

Manabu Kakinohana, MD, PhD^*, Osamu Kakinohana, PhD, Jong Hun Jun, MD, PhD, Martin Marsala, MD, Kenneth J. Davison, MD, and Kazuhiro Sugahara, MD, PhD^*

*Department of Anesthesiology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan; Department of Anesthesiology, University of California, San Diego, California; Department of Anesthesiology, Hanyang University College of Medicine, Seoul, Korea; and Department of Anesthesiology, Massachusetts General Hospital, Boston, Massachusetts

Address correspondence and reprint requests to Manabu Kakinohana, MD, PhD, Department of Anesthesiology, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan. Address e-mail to mnb-shk{at}ryukyu.ne.jp.

We investigated the relationship between the degeneration of spinal motor neurons and activation of N-methyl-d-aspartate (NMDA) receptors after neuraxial morphine following a noninjurious interval of aortic occlusion in rats. Spinal cord ischemia was induced by aortic occlusion for 6 min with a balloon catheter. In a microdialysis study, 10 µL of saline (group C; n = 8) or 30 µg of morphine (group M; n = 8) was injected intrathecally (IT) 0.5 h after reflow, and 30 µg of morphine (group SM; n = 8) or 10 µL of saline (group SC; n = 8) was injected IT 0.5 h after sham operation. Microdialysis samples were collected preischemia, before IT injection, and at 2, 4, 8, 24, and 48 h of reperfusion (after IT injection). Second, we investigated the effect of IT MK-801 (30 µg) on the histopathologic changes in the spinal cord after morphine-induced spastic paraparesis. After IT morphine, the cerebrospinal fluid (CSF) glutamate concentration was increased in group M relative to both baseline and group C (P < 0.05). This increase persisted for 8 hrs. IT MK-801 significantly reduced the number of dark-stained -motoneurons after morphine-induced spastic paraparesis compared with the saline group. These data indicate that IT morphine induces spastic paraparesis with a concomitant increase in CSF glutamate, which is involved in NMDA receptor activation. We suggest that opioids may be neurotoxic in the setting of spinal cord ischemia via NMDA receptor activation.

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