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Neural Sensitization: The Medical Key to Treatment of Chemical Injury (pg 3)

Biochemical Vicious Cycle

  • Neural sensitization occurs by excess inducible nitric oxide.3 This can result from exposure to irritants and/or particle exposure3 and from other chemicals as discussed below.
  • Neural sensitization can also occur by excess activity of brain and nerve cell NMDA (N-methyl-D-aspartate), which then increases brain and other organ (inducible) nitric oxide (NO). 8,16,17
  • When this nitric oxide is increased, especially chronic or repeatedly, free radicals are formed from the vicious biochemical cycle set in motion. Free radicals are substances that damage body cells and organs.18 This cycle is shown in the chemical diagram on page 13.

Below is a detailed discussion of the vicious cycle along with the substances medically documented to control it. This forms the scientific basis for treatment. For more treatment details refer to PRACTICAL GUIDE FOR TREATING CHEMICAL INJURY (being revised).

Inducible Nitric Oxide

The cycle begins with inducible nitric oxide (iNOS).1,3,4 Bioactive B12 works well for reducing excess iNOS.19,20 Methylcobalamin is a bioactive form and more neurocalming than hydroxocobalamin. Cyanocobalamin should not be used.

Nitric oxide also damages the first detoxification step,21 allowing chemicals and many drugs to build up more in the body. This further increases inflammation.

Exhaled nitric oxide is a medically accepted marker of airway inflammation.4 Excess nitric oxide impairs the body’s energy capacity13 and can cause death of energy structures (mitochondria).13 These mitochondrial changes can lead to fatigue.

Mitochondria are structures in body cells that generate energy by producing ATP. Mitochondrial damage has been documented in the vast majority of patients with chronic illness from chemical injury.22 This is a major cause of their fatigue.

When nitric oxide is increased too much, there can be a decrease in body defense antioxidants such as SOD (superoxide dismutase), catalase and glutathione peroxidase.23 Healing substances are needed to help these body protections function better.24

Peroxynitrite Free Radicals

Inducible nitric oxide forms a tissue damaging free radical known as peroxynitrite.2,8,25,26 This then forms even more nitric oxide. See diagram for biochemical details.

Peroxynitrite is a highly potent free radical that damages proteins,13 including enzymes, lipids (brain and cell walls), mitochondrial (energy producing) membranes, ribosomal (protein making) membranes, cell messaging membranes (RNA, etc.) and genetic (DNA) membranes.27 Peroxynitrite weakens the blood-brain barrier, allowing chemicals to enter the brain more readily.

This vicious cycle with increased nitric oxide and peroxynitrite can cause brain cell death and neurodegenerative disease.8,13,26,29-32

Antioxidants such as high gamma Vitamin E (tocopherols) reduce peroxynitrite damage in lipid membranes.33,34 In different cell organ locations, glutathione,  Vitamin C (ascorbic acid),14,38 and alpha lipoic acid39,40 also help protect against these effects. For glutathione function, the body needs selenium 24,41,42 and Vitamin B2 43,44 to help heal damage.

Superoxide Free Radicals

Superoxide free radical reacts with nitric oxide, which then increases peroxynitrite. Excess superoxide can damage the mitochondria (energy production) and other body cells. Superoxide is reduced by the body’s protective enzyme system, SOD (superoxide dismutase). SOD needs minerals zinc, copper and manganese (in proper ratio) to function.24,45,46

Damage to Mitochondria/Energy Structures

Peroxynitrite damages mitochondria and thus also depletes energy ATP,1,13,47 which then further increases sensitization by excess action of NMDA.32,48 Lack of adequate mitochondrial antioxidants damages the mitochondria and forms more peroxynitrite.49

The mitochondria need adequate nutrients to function well to help stop the vicious cycle. These include thiamine, niacin, pantothenate and biotin24,50-53 as well as coenzyme Q1040,54-56 and acetylcarnitine.57-60 Chromium helps glucose enter the cell to be burned for energy, reducing diabetic risk and hunger cravings/obesity. Adequate omega-3 essential fats (EPA/DHA) also helps reduce insulin resistance,61,62 thus helping glucose enter the cell to generate energy.

NMDA (N-methyl-D aspartate) Receptor

NMDA is a neuroexcitation receptor.18 When activated, it increases nitric oxide, peroxynitrite, and other free radicals. 13,63,64

Magnesium calms the NMDA overactivation.65-67 Magnesium is further depleted by body acidity caused by inflammation.24

Pyridoxal phosphate B6 helps form GABA,68 and taurine supports GABA69 and is neurocalming,70 reducing NMDA adverse effects.


Neural sensitization thus involves self-perpetuating excess brain/nerve cell neuroexcitation response to further chemical exposure.71,72 Since nerve cells communicate with all body organs, increased inflammation can involve many organs. This can cause hyperactivity in children and a feeling of being “wired” in all ages, despite fatigue, as well as other changes discussed above.

Antioxidant function in general is usually reduced in chemically ill patients,22 and increased lipid peroxides and other damaging free radicals are common.73 These cause ongoing damage if not corrected by the above medical treatment and environmental controls.

Without adequate antioxidant protection, there is increased risk of inflammation and degenerative diseases, lung damage,74,75 and other organ injury.

The vicious cycle must therefore be interrupted to the maximum extent feasible. Symptoms of sensitization “reactions” 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.22,73,77 Thus masking/blocking symptoms of these cycles by drugs is not recommended because it allows silent damage and patient deterioration. It does not heal the disturbed biochemical mechanism. This is like turning off the battery warning light without fixing the battery.

For effective treatment, the frequency of intake of ingredients must be adequate to CONTINUALLY interrupt the biochemical vicious cycle. Also, interruption in taking protocol ingredients significantly delays the ability to interrupt the biochemical cycle.

Medical References (footnotes)--Neural Sensitization: The Key to Medical Treatment

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