Dynorphin-A-(1-13) antagonizes morphine analgesia in the brain and potentiates morphine analgesia in the spinal cord.
Intrathecal injection of subanalgesic doses of morphine (7.5 nmol) and dynorphin-A-(1-13) (1.25 nmol) in combination resulted in a marked analgesic effect as assessed by tail flick latency in the rat. The analgesic effect of the composite dynorphin/morphine was dose-dependent in serial dilutions so that a composition of 1/8 of the analgesic dose of dynorphin and 1/3 that of morphine produced an analgesic effect equipotent to full dose of either drug applied separately. The analgesic effect induced by dynorphin/morphine mixture was not accompanied by motor dysfunction and was easily reversed by a small dose (0.5 mg/kg) of naloxone. Contrary to the augmentatory effect of dynorphin on morphine analgesia in the spinal cord, intracerevroventricular (ICV) injection of 20 nmol of dynorphin-A-(1-13) exhibited a marked antagonistic effect on the analgesia produced by morphine (120 nmol, ICV). The theoretical considerations and practical implications of the differential interactions between dynorphin-A-(1-13) and morphine in the brain versus spinal cord are discussed.
Ren
M F
MF
Lu
C H
CH
Han
J S
JS
D000698:Analgesia; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002552:Cerebral Ventricles / Q000502:physiology; D004357:Drug Synergism; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007276:Injections, Intraventricular; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009928:Organ Specificity; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D009294:Narcotics; D010446:Peptide Fragments; D009270:Naloxone; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine