Canadian Journal of Anesthesia

, Volume 53, Issue 12, pp 1180–1185 | Cite as

Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats

  • Alain C. Van Elstraete
  • Philippe Sitbon
  • Jean -Xavier Mazoit
  • Marc Conti
  • Dan Benhamou
Regional Anesthesia and Pain



Magnesium exerts a physiological block of the ion channel on the N-methyl-D-aspartate receptor, and may therefore prevent the induction of central sensitization. The purpose of this study was to assess whether systemic magnesium can prevent long-lasting hyperalgesia induced by sc fentanyl administration in uninjured rats.


Long-lasting hyperalgesia was induced in male Sprague Dawley rats with sc fentanyl (four injections, 60 μg·kg−1 per injection at 15-min intervals). Magnesium sulphate (100 mg·kg−1) was injectedip 30 min prior to the first sc fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure test) was assessed for several days after injections.


Subcutaneous fentanyl led to delayed hyperalgesia associated with a decrease in the nociceptive threshold lasting two days (35% decrease for the maximum effect). Intraperitoneal magnesium sulphate partially but significantly (P < 0.05) prevented the delayed decrease in the nociceptive threshold following sc administration of fentanyl.


This study shows that magnesium may prevent the delayed and prolonged hyperalgesia following fentanyl administration in rats.


Fentanyl Neuropathic Pain Magnesium Concentration Magnesium Sulphate Morphine Tolerance 

L’effet protecteur de l’administration préalable de magnésium sur l’hyperalgésie secondaire produite par le fentanyl chez le rat



Le magnésium exerce un blocage physiologique du récepteur N-méthyl-D-aspartate, et peut donc prévenir l’induction d’une sensibilisation centrale. Le but de cette étude était de déterminer si l’administration systémique de magnésium pouvait prévenir l’hyperalgésie prolongée induite par le fentanyl sc chez le rat naïf.


Une hyperalgésie prolongée était induite chez le rat mâle Sprague Dawley avec du fentanyl sc (quatre injections, 60 μg·kg−1 par injection à 15 min d’intervalle). Du sulfate de magnésium (100 mg·kg−1) était injecté par voie ip 30 min avant la première injection de fentanyl. La sensibilité aux stimuli nociceptifs (paw-pressure test) était évaluée durant plusieurs jours après les injections.


Le fentanyl a entraîné une hyperalgésie prolongée associée à une diminution du seuil nociceptif durant deux jours (diminution de 35 % de l’effet maximum). L’administration ip de sulfate de magnésium a prévenu partiellement mais significativement (P < 0,05) la diminution du seuil nociceptif secondaire à l’administration sc de fentanyl.


Cette étude démontre que le magnésium peut prévenir l’hyperalgésie secondaire et prolongée après administration de fentanyl chez le rat.


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Copyright information

© Canadian Anesthesiologists 2006

Authors and Affiliations

  • Alain C. Van Elstraete
    • 1
  • Philippe Sitbon
    • 1
  • Jean -Xavier Mazoit
    • 1
  • Marc Conti
    • 1
  • Dan Benhamou
    • 1
  1. 1.Department of Anesthesiology and Biochemistry Laboratory, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, and the Anesthesia Laboratory UPRES-EA3540Faculté de Médecine du Kremlin-Bicêtre Université Paris-SudLe Kremlin-BicêtreFrance

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