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 magnesi um deficiency results from the sum of direct cellular effects and of local and systemic mediated effects inducing depolarization and NHE. Direct effec ts associate decreased energy and cationic gradient with disturbances in Ca distribution, decreased second messenger nucleotidic ratio and increased s usceptibility to peroxidation. Local mediated effects associate increased a ctivity of excitatory neuromediators: acetylcholine, catecholamines and ion otropic - (NMDA and non-NMDA) - receptors of excitatory aminoacids (EAA], w ith decreased activity of inhibitory neuromediators: GABA, taurine, glutaur ine, adenosine and K receptors of opioids. Systemic mediated effects associ ate increased production of inflammatory mediators: neuropeptides, prostano ids, cytokines Th 1, aldehydes with decreased activity of oxidant and antia ldehyde defences. Compensatory factors instrumental in the latency of NHE due to magnesium de ficiency may also be direct or mediated. Increased intracellular pH, modifi cations of Ca and Mg binding proteins, increase in 'magnesium-like' polyami nes, stimulation of cellular antioxidant system; decreased activity of EAA metabotropic receptors and of opioid mu land delta] receptors, increased ac tivity of inhibitory neuromediators, increased production of anti-inflammat ory mediator such as cytokines Th 2, stimulation of systemic antioxidant an d antialdehyde defences. A lot of diverse compounds are able to palliate symptomatic NHE due to magn esium deficiency either by pharmacodynamic effects or through physiopatholo gical intervention. The efficiency of these treatments can be evaluated on multiple disparate parameters. The pattern of NHE due to magnesium deficien cy differs according to species, strains, gender, age and intensity of magn esium deficiency. For example: hot plate test showed a hypoalgesia 'morphin e-like' pattern induced by magnesium deficiency cured by magnesium acetylta urinate in mice whilst paw pressure test showed a hyperalgic pattern caused by magnesium deficiency cured by dizolcipine in rats. Now it seems difficu lt 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 sympt omatic and latent forms and stresses the complexity of the physiopathologic al mechanisms of central NHE due to magnesium deficiency.