Temporal dissociation of recovery from antinociceptive and motor effects following intrathecal administration of a selective mu-opioid agonist.
In this series of studies, the antinociceptive and motor side effects associated with intrathecal administration of the selective mu-opioid agonist, DAMGO, were evaluated in the same rat. The Randall-Selitto paw-withdrawal test was used to measure mechanical nociceptive threshold, and an accelerating Rotarod treadmill was used to evaluate motor coordination. In the first experiment (N = 48), intrathecal administration of DAMGO produced dose-dependent increases in mechanical nociceptive thresholds that correlated with decreases in motor coordination. In the second experiment (N = 8), intrathecal administration of naloxone (5 micrograms) reversed both the antinociceptive effects and the motor deficits produced by 5 micrograms of intrathecal DAMGO. In the third experiment (N = 13), following administration of the highest dose of DAMGO (5 micrograms) as part of a cumulative dose response curve, paw-withdrawal and motor coordination testing were continued at 45-minute intervals for a period of 225 minutes. DAMGO-induced deficits in motor coordination recovered significantly sooner than nociceptive responses. These data provide support for the suggestion that the motor as well as antinociceptive effects of spinal opioids are mediated through an action at an opioid receptor, but that these two effects may be mediated by different mechanisms.
Miaskowski
C
C
School of Nursing, University of California, San Francisco.
Franck
L S
LS
Putris
J
J
Levine
J D
JD
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009048:Motor Skills / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000145:classification / Q000187:drug effects; D013997:Time Factors
D000700:Analgesics; D004745:Enkephalins; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone