Neural Sensitization By Dr Martin Pall


Neural Sensitization



Neural sensitization occurs by activation of brain and nerve cell N-methyl-D-aspartate(NMDA), which then increases brain nitric oxide (NO).1,2,3 Several vicious biochemical cycles are then set in motion.  Nitric oxide forms a tissue damaging free radical known as peroxynitrite.2,4,5,6  Peroxynitrite depletes energy TP,7,8 which then further increases the sensitization of NMDA. 9,10


Chemical exposure can induce sensitization.  Pesticides such as organophosphates inhibit acetylcholine, acitivating muscarinic receptors, which increase nitric oxide.  Formaldehyde activates NMDA.1,11

Petrochemicals (VOC’s, solvents) disrupt energy production in the nitochondria, increase super oxide which increases peroxynitrite.12 This can then increase tissue-damaging free radicals in the brain.13 Mitochondrial disruption occurs in chemically injured patients.14 Petrochemicals and many other chemicals are irritants15 that with exposure can cause inflammation.  Inflammation of sufficient duration can lead to chronic neurogenic inflammation.16 Inflammation results in increased cytokines, free radicals and elevated nitric oxide.


Neural sensitization is thus associated with self-perpetuating neuroexcitation and excessive response to further chemical exposure.11,17   This NMDA activation with increased nitric oxide and peroxynitrite can cause brain cell death and neurogenerative disease.2,6,10,18,19,20  Peroxynitrite also weakens the blood-brain barrier, allowing chemicals to enter the brain more readily.21  Nitric oxide also damages the first detoxification step involving the cytochrome p450 system,22 allowing chemicals (and many drugs) to build up more in the body.


This vicious cycle MUST therefore be interrupted to the maximum extent feasible.  Because the resulting symptoms of sensitization are warnings that other more silent toxic-induced organ damage of the liver, pancreas, immune system, adrenals, mitochondria and other organs can be also occurring,16,23,24

masking/blocking symptoms of this cycle is not recommended without healing the disturbed biochemical mechanism.  (This would be like turning off a battery warning light without fixing the battery.)  Cobalamine(B12) is a nitric oxide scavenger and deficient in the majority of chemically ill patients.  The cyano form is not recommended (these patients don’t need cyanide and the hydroxy and methyl forms work much better in the brain and nerve cells). Superoxide dismutase is deficient in a significant portion of chemically ill patients and its cofactors, copper, zinc, and manganese must be adequate.  These are often reduced in chemically injured patients and should be tested and replaced in well-absorbed and transported forms, for example, picolinates.  Antioxidant function is usually inadequate in chemically ill patients,23  and increased lipid peroxides and other free radicals are common.


Intervention to help reduce this vicious biochemical cycle includes: methyl or hydroxycobalamine sublingually or I.M. (not oral due to poor absorption), general antioxidants (C, E, selenium), glutathione by nebulizer due to poor oral absorption, and ample alpha lipoic acid to reactivate the glutathione in the many damaged lipid tissues (cell membranes, mitochondria, lymph, brain, etc,).  Trimethyl glycine is recommended as a methyl donor to reduce the effects of peroxynitrite.  Magnesiuim should be ample because deficiency is very common with toxic injury and adequate magnesium decreases NMDA activiation.  Peroxynitrite scavengers such as a mixture of caretenoids are also recommended.  Carentenoids tend to be more organ-specific.  An inclusion of gingko (brain), silimarin (liver), bilberry (collagen stabilizing, capillary permeability, vision), cranberry (urinary) and other mixed caretenoids is recommended.


Mineral levels should be measured and followed by intercellular (eg.RBC) or lipid functional (eg. Lymphocyte mitogenesis, a SpectraCell technology).  Functional lymphocyte evaluaion and follow-up of glutathione, lipoic acid, total antioxidant function, C, E and zinc is also recommended. At this time this technology is only available through Spectra cell laboratory.


None of the above is a substitute for exposure controls at home, work and /or places where the person spends most of their time.  Humans are social beings, and these measures above gradually increase the person’s ability to enjoy the company of others and use public places.  When society is adequately informed and takes public health accommodation measures to reduce irritants and toxins in personal products and public places, this further promotes health and reduces sensitization.



      Solvents, Voc’s         Pesticides (OP,carbamates)




         NMDA              Nitric Oxide        Inflammation,

                                              Tissue injury


     Superoxide      Neural       Peroxynitrite





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