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Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α.
Pain Physician. 2013 Sep-Oct; 16(5):E563-75.PP

Abstract

BACKGROUND

Clinical studies have shown that about two-thirds of patients with chronic pain suffer from short-term memory (STM) deficits and an effective drug for treatment of the neurological disorder is lacking at present.

OBJECTIVE

We tested whether chronic oral application of magnesium L-threonate (MgT), which has been shown to improve memory in normal and aging animals by elevating Mg2+ in the brain, could prevent or restore the STM deficits induced by spared nerve injury (SNI), an animal model of chronic neuropathic pain. The mechanisms underlying the effect of MgT on STM deficits were also investigated.

STUDY DESIGN

The experiments were conducted in a random and double-blind fashion in adult male rats. MgT was administrated via drinking water at a dose of 609 mg/kg/d for 2 weeks, starting either one week before SNI (preventative group) or one week after SNI (therapeutic group), and water without the drug served as control.

METHODS

STM was accessed with a novel object recognition test (NORT), followed by recording of long-term potentiation (LTP) in the hippocampus in vivo and the measurement of the expression of tumor necrosis factor-α (TNF-α) with Western Blot or Immunohistochemistrical staining, a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor (NMDAR) currents were recorded with patch clamp in CA1 neurons in acute and cultured hippocampal slices.

RESULT

We found that chronic oral application of MgT was able to prevent and restore the deficits of STM and of LTP at CA3-CA1 synapses in the hippocampus induced by SNI. Furthermore, both preventative and therapeutic chronic oral application of MgT blocked the up-regulation of TNF-α in the hippocampus, which has been previously shown to be critical for memory deficits. SNI reduced NMDAR current and the effect was dramatically attenuated by elevating extracellular Mg2+ concentration ([Mg2+]○). In cultured hippocampal slices, chronic application of recombinant rat TNF-α (rrTNF-α) for 3 days reduced NMDAR current in a concentration-dependent manner and the effect was again blocked by elevating [Mg2+]○.

LIMITATIONS

We showed that oral application of MgT inhibited the over-expression of TNF-α and rescued the dysfunction of the NMDAR, but the causal relationship between them remains elusive.

CONCLUSIONS

Our data suggested that oral application of MgT was able to prevent and restore the STM deficits in an animal model of chronic neuropathic pain by reversing the dysfunction of the NMDAR, and normalization of TNF-α expression may play a role in the effect. Oral application of MgT may be a simple and potent means for handling this form of memory deficit.

Authors+Show Affiliations

Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24077207

Citation

Wang, Jun, et al. "Magnesium L-threonate Prevents and Restores Memory Deficits Associated With Neuropathic Pain By Inhibition of TNF-α." Pain Physician, vol. 16, no. 5, 2013, pp. E563-75.
Wang J, Liu Y, Zhou LJ, et al. Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α. Pain Physician. 2013;16(5):E563-75.
Wang, J., Liu, Y., Zhou, L. J., Wu, Y., Li, F., Shen, K. F., Pang, R. P., Wei, X. H., Li, Y. Y., & Liu, X. G. (2013). Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α. Pain Physician, 16(5), E563-75.
Wang J, et al. Magnesium L-threonate Prevents and Restores Memory Deficits Associated With Neuropathic Pain By Inhibition of TNF-α. Pain Physician. 2013 Sep-Oct;16(5):E563-75. PubMed PMID: 24077207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α. AU - Wang,Jun, AU - Liu,Yong, AU - Zhou,Li-Jun, AU - Wu,Ying, AU - Li,Fei, AU - Shen,Ka-Feng, AU - Pang,Rui-Ping, AU - Wei,Xu-Hong, AU - Li,Yong-Yong, AU - Liu,Xian-Guo, PY - 2013/10/1/entrez PY - 2013/10/1/pubmed PY - 2014/5/23/medline SP - E563 EP - 75 JF - Pain physician JO - Pain Physician VL - 16 IS - 5 N2 - BACKGROUND: Clinical studies have shown that about two-thirds of patients with chronic pain suffer from short-term memory (STM) deficits and an effective drug for treatment of the neurological disorder is lacking at present. OBJECTIVE: We tested whether chronic oral application of magnesium L-threonate (MgT), which has been shown to improve memory in normal and aging animals by elevating Mg2+ in the brain, could prevent or restore the STM deficits induced by spared nerve injury (SNI), an animal model of chronic neuropathic pain. The mechanisms underlying the effect of MgT on STM deficits were also investigated. STUDY DESIGN: The experiments were conducted in a random and double-blind fashion in adult male rats. MgT was administrated via drinking water at a dose of 609 mg/kg/d for 2 weeks, starting either one week before SNI (preventative group) or one week after SNI (therapeutic group), and water without the drug served as control. METHODS: STM was accessed with a novel object recognition test (NORT), followed by recording of long-term potentiation (LTP) in the hippocampus in vivo and the measurement of the expression of tumor necrosis factor-α (TNF-α) with Western Blot or Immunohistochemistrical staining, a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor (NMDAR) currents were recorded with patch clamp in CA1 neurons in acute and cultured hippocampal slices. RESULT: We found that chronic oral application of MgT was able to prevent and restore the deficits of STM and of LTP at CA3-CA1 synapses in the hippocampus induced by SNI. Furthermore, both preventative and therapeutic chronic oral application of MgT blocked the up-regulation of TNF-α in the hippocampus, which has been previously shown to be critical for memory deficits. SNI reduced NMDAR current and the effect was dramatically attenuated by elevating extracellular Mg2+ concentration ([Mg2+]○). In cultured hippocampal slices, chronic application of recombinant rat TNF-α (rrTNF-α) for 3 days reduced NMDAR current in a concentration-dependent manner and the effect was again blocked by elevating [Mg2+]○. LIMITATIONS: We showed that oral application of MgT inhibited the over-expression of TNF-α and rescued the dysfunction of the NMDAR, but the causal relationship between them remains elusive. CONCLUSIONS: Our data suggested that oral application of MgT was able to prevent and restore the STM deficits in an animal model of chronic neuropathic pain by reversing the dysfunction of the NMDAR, and normalization of TNF-α expression may play a role in the effect. Oral application of MgT may be a simple and potent means for handling this form of memory deficit. SN - 2150-1149 UR - https://www.unboundmedicine.com/medline/citation/24077207/Magnesium_L_threonate_prevents_and_restores_memory_deficits_associated_with_neuropathic_pain_by_inhibition_of_TNF_α_ L2 - http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=16&page=E563 DB - PRIME DP - Unbound Medicine ER -