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

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 μg·kg^-1 per injection at 15-min intervals). Magnesium sulphate (100 mg·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.