JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fairbanks, C. A.
Right arrow Articles by Wilcox, G. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fairbanks, C. A.
Right arrow Articles by Wilcox, G. L.

Vol. 288, Issue 3, 1107-1116, March 1999

Spinal Antinociceptive Synergism between Morphine and Clonidine Persists in Mice Made Acutely or Chronically Tolerant to Morphine1

Carolyn A. Fairbanks and George L. Wilcox

Department of Pharmacology (C.A.F., G.L.W.), Graduate Program in Neuroscience (G.L.W.), University of Minnesota, Minneapolis, Minnesota

Morphine (Mor) tolerance has been attributed to a reduction of opioid-adrenergic antinociceptive synergy at the spinal level. The present experiments tested the interaction of intrathecally (i.t.) administered Mor-clonidine (Clon) combinations in mice made acutely or chronically tolerant to Mor. ICR mice were pretreated with Mor either acutely (40 nmol i.t., 8 h; 100 mg/kg s.c., 4 h) or chronically (3 mg/kg s.c. every 6 h days 1 and 2; 5 mg/kg s.c. every 6 h days 3 and 4). Antinociception was detected via the hot water (52.5°C) tail-flick test. After the tail-flick latencies returned to baseline levels, dose-response curves were generated to Mor, Clon, and Mor-Clon combinations in tolerant and control mice. Development of tolerance was confirmed by significant rightward shifts of the Mor dose-response curves in tolerant mice compared with controls. Isobolographic analysis was conducted; the experimental combined ED50 values were compared statistically against their respective theoretical additive ED50 values. In all Mor-pretreated groups, the combination of Mor and Clon resulted in significant leftward shifts in the dose-response curves compared with those of each agonist administered separately. In all tolerant and control groups, the combination of Mor and Clon produced an ED50 value significantly less than the corresponding theoretical additive ED50 value. Mor and Clon synergized in Mor-tolerant as well as in control mice. Spinally administered adrenergic/opioid synergistic combinations may be effective therapeutic strategies to manage pain in patients apparently tolerant to the analgesic effects of Mor.

0022-3565/99/2883-1107$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
G. Horvath, G. Kekesi, I. Dobos, W. Klimscha, and G. Benedek
Long-Term Changes in the Antinociceptive Potency of Morphine or Dexmedetomidine After a Single Treatment
Anesth. Analg., September 1, 2005; 101(3): 812 - 818.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
Y. Grabovsky and R. J. Tallarida
Isobolographic Analysis for Combinations of a Full and Partial Agonist: Curved Isoboles
J. Pharmacol. Exp. Ther., September 1, 2004; 310(3): 981 - 986.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
S. Sator-Katzenschlager, E. Deusch, P. Maier, A. Spacek, and H. G. Kress
The Long-Term Antinociceptive Effect of Intrathecal S(+)-Ketamine in a Patient with Established Morphine Tolerance
Anesth. Analg., October 1, 2001; 93(4): 1032 - 1034.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. J. Tallarida
Drug Synergism: Its Detection and Applications
J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 865 - 872.
[Abstract] [Full Text]

Home page
 J. Neurosci.Home page
L. M. Bohn, F. Xu, R. R. Gainetdinov, and M. G. Caron
Potentiated Opioid Analgesia in Norepinephrine Transporter Knock-Out Mice
J. Neurosci., December 15, 2000; 20(24): 9040 - 9045.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. J. Garrido, M. Valle, M. A. Campanero, R. Calvo, and I. F. Trocóniz
Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (-)-O-Desmethyltramadol, in Rats
J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 352 - 359.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. A. Fairbanks and G. L. Wilcox
Moxonidine, a Selective alpha 2-Adrenergic and Imidazoline Receptor Agonist, Produces Spinal Antinociception in Mice
J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 403 - 412.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.