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Unlike the superadditive interaction between magnesium salt and methadone, copper ions give rise only to an additive effect in the public speech formalin test when administered together with methadone. Although it remains yet uncertain the mechanism underlying the ability of magnesium sulfate to exert jump into conclusions synergistic action upon the methadone antinociceptive effect, this issue could constitute a potential basis for future clinical applications addressed to lower methadone dosing together with a lowering of its side-effects.

As pointed out elsewhere (Erichsen et al. However, therapeutic guidelines relegate strong opioids, including methadone, to third-line therapy in neuropathic pain mainly because of safety concerns (Finnerup et al. Drug combination strategies aimed to reduce methadone dosingand therefore its side-effectscould be a promising therapeutic approach to optimize opioid analgesia under neuropathic pain conditions, provided the drug jump into conclusions with jump into conclusions does not give rise to important side-effects by its own.

To this end, magnesium salts probably represent the best alternative, since the European Jump into conclusions Safety Authority (EFSA) of the European Union states that the upper limit for magnesium (i.

Although further studies are necessary to examine in detail the mechanism underlying the synergistic interaction between magnesium ions and methadone, it can be concluded that this association could represent a potential therapeutic strategy aimed to treat some forms of chronic pain in humans, which deserves more investigation in clinical settings. The animal study was reviewed and approved by Bioethics Committee of the University of Santiago de Chile.

TP and LC provided ideas or concepts for definition of intellectual context, particularly designed and performed the experiments. VG, VC, and TP performed research. VG, AH, TP, and LC analyzed data. AH and LC wrote the paper. All authors of this paper have read and approved the final version of the manuscript.

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