Magnesium sulfate potentiates morphine antinociception at the spinal level

Intrathecal magnesium sulfate coinfusion with morphine increases antinocice ption in normal rats; however, because magnesium also delays the onset of t olerance, it is not clear whether this additional antinociception is a resu lt of potentiated analgesia or tolerance abatement. We examined the antinoc iceptive interaction of intrathecal (IT) bolus magnesium sulfate and morphi ne in morphine naive rats and those with mechanical allodynia after a surgi cal incision. After intrathecal catheter implantation, rats were given prei njections of magnesium or saline, followed by injections of morphine or sal ine. In morphine naive rats, IT bolus magnesium sulfate 281 and 375 mu g fo llowed by IT morphine 0.25 or 0.5 nmol enhanced peak antinociception and ar ea under the response versus time curve two-to-three-fold in the tail-flick test as compared with morphine alone. Likewise, in rats with incisional pa in, IT bolus magnesium sulfate 188 and 375 mu g followed by morphine 0.5 nm ol reduced mechanical allodynia, whereas morphine 0.5 nmol alone did not. T his study suggests that IT magnesium sulfate potentiates morphine at a spin al site of action. Implications: Magnesium sulfate potentiates morphine ana lgesia when coadministered intrathecally in normal rats, and in an animal m odel of mechanical allodynia after a surgical incision. These results sugge st that intrathecal administration of magnesium sulfate may be a useful adj unct to spinal morphine analgesia.