Physiopathology of symptomatic and latent forms of central nervous hyperexcitability due to magnesium deficiency: a current general scheme.

Symptomatic forms of central nervous hyperexcitability (NHE) due to magnesium deficiency results from the sum of direct cellular effects and of local and systemic mediated effects inducing depolarization and NHE. Direct effects associate decreased energy and cationic gradient with disturbances in Ca distribution, decreased second messenger nucleotidic ratio and increased susceptibility to peroxidation. Local mediated effects associate increased activity of excitatory neuromediators: acetylcholine, catecholamines and ionotropic - (NMDA and non-NMDA) - receptors of excitatory aminoacids (EAA), with decreased activity of inhibitory neuromediators: GABA, taurine, glutaurine, adenosine and K receptors of opioids. Systemic mediated effects associate increased production of inflammatory mediators: neuropeptides, prostanoids, cytokines Th 1, aldehydes with decreased activity of oxidant and antialdehyde defences. Compensatory factors instrumental in the latency of NHE due to magnesium deficiency may also be direct or mediated. Increased intracellular pH, modifications of Ca and Mg binding proteins, increase in 'magnesium-like' polyamines, stimulation of cellular antioxidant system; decreased activity of EAA metabotropic receptors and of opioid mu (and delta) receptors, increased activity of inhibitory neuromediators, increased production of anti-inflammatory mediator such as cytokines Th 2, stimulation of systemic antioxidant and antialdehyde defences. A lot of diverse compounds are able to palliate symptomatic NHE due to magnesium deficiency either by pharmacodynamic effects or through physiopathological intervention. The efficiency of these treatments can be evaluated on multiple disparate parameters. The pattern of NHE due to magnesium deficiency differs according to species, strains, gender, age and intensity of magnesium deficiency. For example: hot plate test showed a hypoalgesia 'morphine-like' pattern induced by magnesium deficiency cured by magnesium acetyltaurinate in mice whilst paw pressure test showed a hyperalgic pattern caused by magnesium deficiency cured by dizolcipine in rats. Now it seems difficult to rank hierarchically the various physiopathological mechanisms of NHE due to magnesium deficiency. But the proposed general scheme of the factors controlling this NHE provides a possible explanation of both diffuse symptomatic and latent forms and stresses the complexity of the physiopathological mechanisms of central NHE due to magnesium deficiency.