Depression of the flexor reflex by systemic morphine increases in chronically spinalized rats.
The effect of i.v. morphine on the spinal nociceptive flexor reflex was examined in decerebrate, unanesthetized rats in which the spinal cord was acutely or chronically transected. In acutely spinalized rats i.v. morphine dose dependently depressed the flexor reflex with an ED50 of 1.4 mg/kg. In rats in which the spinal cord was transected 1-3 days prior to the electrophysiological experiments, i.v. morphine had a similar depressive effect (ED50 = 1.1 mg/kg). However, 4-6 days after spinalization there was a 4-fold increase in morphine's depressive effect (ED50 = 0.35 mg/kg). The sensitivity to morphine was further increased 7-10 days post-spinalization with ED50 of 0.17 mg/kg. This supersensitivity was maintained up to 30-60 days. The reflex depression caused by morphine in both acutely and chronically spinalized rats could be reversed by naloxone. Morphine i.v. did not influence the monosynaptic reflex in either acutely or chronically spinalized rats. The present results support the clinical finding that patients with spinal lesions have an increased sensitivity to the antinociceptive and reflex depressive effects of systemic and intrathecal morphine.
Hao
J X
JX
Department of Clinical Physiology, Karolinska Institute, Huddinge, Sweden.
Wiesenfeld-Hallin
Z
Z
Xu
X J
XJ
D000818:Animals; D003655:Decerebrate State; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D007275:Injections, Intravenous; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000503:physiopathology
D009020:Morphine