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Canadian Journal of Anesthesia

, Volume 53, Issue 9, pp 891–898 | Cite as

Regional Anesthesia and Pain

Ketamine and N-acetylaspartylglutamate peptidase inhibitor exert analgesia in bone cancer pain
  • Osamu SaitoEmail author
  • Tomohiko Aoe
  • Alan Kozikowski
  • Jayaprakash Sarva
  • Joseph H. Neale
  • Tatsuo Yamamoto
General Anesthesia

Abstract

Purpose

Not all bone cancer pain can be effectively treated with current therapies. In the present study, the effects ofip administration of α-2 agonists (dexmedetomidine and clonidine), N-methyl-D-aspartate (NMDA) antagonists (MK-801 and ketamine), an N-acetylaspartylglutamate peptidase inhibitor (ZJ-43), and morphine were examined in a mouse bone cancer pain model.

Methods

A bone cancer pain model was produced by injection of murine sarcoma cells into the medullary cavity of the distal femur. To estimate the level of bone cancer pain, the number of pain-related behaviours induced by repeated applications of a von Frey monofilament (0.166 g) to the site of tumour cells implantation was counted. Drugs were administered two weeks after the implantation.

Results

Morphine produced a significant analgesic effect (P < 0.001 ). The α-2 agonists produced analgesic effects (P < 0.001 ) with an efficacy similar to that of morphine, but only at doses that produced severe sedation. MK-801 had only limited analgesic effects, while ketamine produced an analgesic effect (P < 0.001) with the same efficacy as morphine. ZJ-43 (100 mg·kg-1) had a significant analgesic effect (P < 0.05) and the effect of ZJ-43 was antagonized by the selective group II metabotropic glutamate receptor (mGluR) antagonist.

Conclusion

hese data suggest that α-2 agonists produce an analgesic effect only at a sedative dose and that ketamine, but not MK-801, is associated with an analgesic response without overt side effects. The effect of ZJ-43 is mediated by activating group II mGluRs.

Keywords

Morphine Clonidine Naloxone Analgesic Effect Dexmedetomidine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

La kétamine et un inhibiteur N-acétylaspartylglutamate peptidase exercent une analgésie sur la douleur du cancer des os

Résumé

Objectif

Les douleurs du cancer des os ne sont pas toujours soulagées par les traitements habituels. Dans la présente étude, les effets de l’administration ip d’agonistes α-2 (dexmédétomidine et clonidine), d’antagonistes N-méthyl-D-aspartate (NMDA) (MK-801 et kétamine), d’un inhibiteur de N-acétylaspartylglutamate peptidase (ZJ-43) et de morphine ont été examinés dans un modèle de douleur du cancer des os chez la souris.

Méthode

Un modèle de douleur du cancer des os a été produit en injectant des cellules de sarcome d’Ewing dans la cavité médullaire distale du fémur. Pour évaluer le niveau de douleur, nous avons calculé le nombre de mouvements reliés à la douleur induite par l’application répétée d’un monofilament von Frey (0,166 g) au site de la tumeur implantée. Les médicaments ont été administrés deux semaines après l’implantation.

Résultats

La morphine a produit une analgésie significative (P < 0,001). Les agonistes α-2 ont produit une analgésie (P < 0,001) similaire à celle de la morphine, mais seulement à des doses produisant une sédation importante. Le MK-801 a eu un effet limité et la kétamine a produit une analgésie aussi efficace que celle de la morphine (P < 0,001). Le ZJ-43 (100 mg·kg-1) a eu un effet analgésique significatif (P < 0,05) contré par l’antagoniste sélectif des récepteurs de glutamate métabotropique (mGluR) de groupe II.

Conclusion

Les agonistes α-2 produisent un effet analgésique à des doses sédatives seulement et la kétamine, mais non le MK-801, est associée à une réaction analgésique sans effets secondaires apparents. L’effet du ZJ-43 origine de l’activation des mGluR de groupe II.

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Copyright information

© Canadian Anesthesiologists 2006

Authors and Affiliations

  • Osamu Saito
    • 1
    Email author
  • Tomohiko Aoe
    • 1
  • Alan Kozikowski
    • 2
  • Jayaprakash Sarva
    • 2
  • Joseph H. Neale
    • 3
  • Tatsuo Yamamoto
    • 1
  1. 1.Department of AnesthesiologyGraduate School of Medicine, Chiba UniversityChiba-shiJapan
  2. 2.Department of Medical ChemistryUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Department of BiologyGeorgetown UniversityWashingtonUSA

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