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Updated: Jul 18, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats
Alain C Van Elstraete1, Philippe Sitbon, Jean-Xavier Mazoit
1Department of Anesthesiology and Biochemistry Laboratory, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, and the Anesthesia Laboratory UPRES-EA3540, Faculté de Médecine du Kremlin-Bicêtre Université Paris-Sud, Le Kremlin-Bicêtre, France. alainvanel@hotmail.com
Purpose:
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.
Methods:
Long-lasting hyperalgesia was induced in male Sprague Dawley rats with sc fentanyl (four injections, 60 microg x kg(-1) per injection at 15-min intervals). Magnesium sulphate (100 mg x kg(-1)) was injected ip 30 min prior to the first sc fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure test) was assessed for several days after injections.
Results:
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.
Conclusions:
This study shows that magnesium may prevent the delayed and prolonged hyperalgesia following fentanyl administration in rats.
