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.
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 muL of saline (group C; n = 8) or 30 mug of morphine (group M; n = 8) was injected intrathecally (IT) 0.5 h after reflow, and 30 mug of morphine (group SM; n = 8) or 10 muL 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 mug) 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 alpha-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.
Kakinohana
Manabu
M
*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.
Kakinohana
Osamu
O
Jun
Jong Hun
JH
Marsala
Martin
M
Davison
Kenneth J
KJ
Sugahara
Kazuhiro
K
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity*; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology*; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D020335:Paraparesis / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000008:administration & dosage*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D020760:Spinal Cord Ischemia / Q000473:pathology*
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D009020:Morphine