Elimination of the antianalgesic action of dynorphin A by spinal transsection in barbital-anesthetized mice.
Previous studies in mice demonstrate that, when dynorphin A (1-17) (Dyn A) is administered intrathecally (i.t.) or released spinally (by administration of clonidine or midazolam i.c.v.), i.t. morphine-induced analgesia was reduced. The present aim was to determine whether this antianalgesic action of Dyn A was the result of a spinal or supraspinal site of action by performing studies in spinally transsected mice. The approach was to use anesthetized, acute spinally transsected mice rather than chronic spinally transsected animals to avoid the need for long-term special animal care. The first part of the study evaluated four nonvolatile general anesthetic agents in an attempt to obtain one that did not affect the antianalgesic action of Dyn A, the release of Dyn A, the analgesic action of i.t. morphine (inhibition of the tail-flick response) or the tail-flick latency by itself. alpha-Chloralose (120 mg/kg), urethane (1 g/kg) and pentobarbital (20 or 40 mg/kg) given i.p. did not meet one or more of these requirements. Barbital 400 mg/kg i.p. met the requirements. In the second part of the study, barbital combined with halothane anesthesia was used to perform acute spinal transsection experiments. As in sham controls, the analgesic action of i.t. morphine was undiminished in spinally transsected animals, which indicated that the inhibition of the tail-flick response produced by i.t. morphine was on a spinal reflex response. On the other hand, spinal transsection produced a loss of the action of i.t. Dyn A to antagonize i.t. morphine-induced analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
F S
FS
Department of Pharmacology and Toxicology, Veterans Administration Medical Center, Milwaukee, Wisconsin.
Rady
J J
JJ
Fujimoto
J M
JM
D000698:Analgesia; D000758:Anesthesia; D000818:Animals; D001462:Barbital; D002698:Chloralose / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010424:Pentobarbital; D013116:Spinal Cord / Q000502:physiology*; D014520:Urethane / Q000494:pharmacology
D002698:Chloralose; D014520:Urethane; D001462:Barbital; D004399:Dynorphins; D010424:Pentobarbital