Additive Effect of Combined Application of Magnesium and MK-801 on Analgesic Action of Morphine

Abstract

As previously reported, magnesium ions (Mg²⁺) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg²⁺ behaves like an N-methyl-<smlcap>D</smlcap>-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared with that of MK-801. Acute pain was evoked by mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801 (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to acute stimuli or the streptozotocin hyperalgesia but significantly augmented the analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e. magnesium sulphate and MK-801) were applied concomitantly, a clear additive effect on the analgesic action of morphine occurred in both models of pain. Possible explanations of these observations are discussed.

Magnesium and Morphine in the Treatment of Chronic Neuropathic Pain–A Biomedical Mechanism of Action

“…Some data indicate that PAG stimulation was effective in mechanical allodynia in the animal model of neuropathic pain [50]. As shown in our previous studies [25,51], the gradual development of mechanical hyperalgesia was observed in STZtreated animals (data not shown). We demonstrated a lack of antinociceptive effect upon MRF application alone over 7 consecutive days in animals with persistent neuropathic pain.…”

Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: a double-blind randomized controlled trial

“…It has been reported to potentiate lidocaine [1], induce analgesia during spinal anesthesia [2,3], improve morphine analgesia in animals [4]and humans [5], and reduce postoperative morphine consumption [6,7]. Several trials with different doses, routes, and methods of administration of magnesium have been reported, some with conflicting results [8][9][10][11][12].…”

The effect of metformin on morphine analgesic tolerance and dependence in rats

“…It is well established that activation of NMDA receptors has important role in the development of morphine tolerance and dependence( 30 ). It has been shown that NMDA receptor antagonist such as MK-801 could prevent morphine-induced tolerance and dependence( 31 ). In this regard, a recent investigation by Zhou et al .…”