Intrathecal nicorandil and small-dose morphine can induce spastic paraparesis after a noninjurious interval of spinal cord ischemia in the rat.
We investigated the interaction between nicorandil, a K(+)ATP channel opener, and morphine on motor function after a noninjurious interval of spinal cord ischemia in the rat. Spinal ischemia was induced by aortic occlusion for 6 min with a balloon catheter in Sprague-Dawley rats. All animals received intrathecal (IT) injection of morphine (1-60 microg) 1 h after ischemia. In addition to IT injection of morphine, group M (control), group MN (combination of morphine and nicorandil), and group MNG (combination of morphine, nicorandil, and glibenclamide) received IT saline, nicorandil (10 microg), and both glibenclamide (10 microg) and nicorandil (10 microg) after 150 min of reperfusion, respectively. A quantal bioassay for the effect of IT morphine on neurological function after ischemia was performed to calculate 50% effective dose values (ED50) for inducing paraparesis at 3 h of reperfusion. The ED50 in group M and group MN was 15.1 +/- 4.9 microg and 2.9 +/- 1.0 microg of IT morphine, respectively (P < 0.05). In Group MNG, the dose-response curve shifted back to the right and the ED50 for inducing paraparesis was 11.6 +/- 4.7 microg of IT morphine. The present study demonstrates that IT small-dose morphine combined with nicorandil induces spastic paraparesis after noninjurious interval of spinal cord ischemia in the rat.
Department of Anesthesiology, University of the Ryukyus, Okinwawa, Japan.
Tatsuya
T
Fuchigami
Manabu
M
Kakinohana
Seiya
S
Nakamura
Kenji
K
Murata
Kazuhiro
K
Sugahara
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005905:Glyburide / Q000008:administration & dosage; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D020108:Nicorandil / Q000008:administration & dosage / Q000009:adverse effects*; D020336:Paraparesis, Spastic / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D020760:Spinal Cord Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D013997:Time Factors
D020108:Nicorandil; D009020:Morphine; D005905:Glyburide