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Regional Anesthesia and Pain Control

Magnesium Sulfate Potentiates Morphine Antinociception at the Spinal Level

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Department of Anesthesiology, Rush Medical College at Rush-Presbyterian-St. Luke’s Medical Center, Chicago, Illinois

Anesth. Analg., 90: 913–917, 2000

Because postoperative opioid requirements are reduced by systemic magnesium sulfate, magnesium appears to have a potentiating effect on opioid analgesia. In normal rats, intrathecal (IT) magnesium sulfate coinfusion increases antinociception. Magnesium also delays the onset of tolerance, however, and whether this additional antinociception results from potentiated analgesia or tolerance abatement is uncertain. In this study, the antinociceptive interaction of IT bolus magnesium sulfate and morphine was examined in morphine naive rats and in rats with mechanical allodynia after a surgical incision.

Five days after IT catheter implantation, 158 male Sprague Dawley rats were tested for antinociception. Thermal latencies were measured with a tail-flick apparatus, and motor coordination was evaluated by observing the animals maintain balance on a rotating rod. Tail-flick testing was repeated 15 min after the animals received a randomly assigned injection of magnesium sulfate (375, 281, or 188 μg) or saline. Immediately after testing, an IT injection of morphine sulfate (0.5 or 0.25 nmol) or saline was administered. Antinociceptive testing was then repeated at 15, 30, 45, 60, 90, and 120 min; motor coordination was assessed at 25 min. In a separate group of 60 rats with an IT catheter, mechanical allodynia was tested by using Von Prey filaments applied to an area of the hind paw adjacent to a surgical incision. The animals were assessed again after receiving IT bolus injections of magnesium sulfate (375, 188, or 94 μg) or saline, followed by IT injection of morphine (0.5 nmol) or saline.

Compared with morphine alone, an IT bolus of magnesium sulfate (281 and 375 μg) followed by IT morphine (0.25 or 0.5 nmol) increased both the peak antinociception and the area under the response vs. time curve in morphine naive rats. All animals were able to stay on the rotating rod for a normal amount of time. In the mechanical allodynia model, morphine 0.5 nmol alone and magnesium sulfate 375 μg by itself were without effect. The withdrawal threshold was increased when magnesium sulfate (188 and 375 μg) was combined with morphine (0.5 nmol).

In both studies, magnesium sulfate was found to potentiate morphine analgesia. The IT administration of magnesium sulfate may be a useful adjunct to neuraxial opioid analgesia.


This animal study suggests that magnesium administered intrathecally potentiates the analgesic effects of opioids. Magnesium administered in such a fashion did not result in any histologic abnormalities and all animals had complete neurologic recovery. The authors do not speculate on mechanism(s) of action. They note that their earlier work using magnesium alone did not result in analgesia. I hope to see further work from the authors examining the mechanism of analgesia.

Ferne B. Sevarino M.D.

© 2001 Lippincott Williams & Wilkins, Inc.