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

 

Biochemistry of the Vicious Cycles

Neural sensitization occurs by excess activity of brain and nerve cell (NMDA) N-methyl-D-aspartate, which then increases brain and other cell nitric oxide (NO). Inflammation also causes increase in nitric oxide. This can result from exposure to irritants and/or particle exposure,5 and other chemicals as discussed below.

When nitric oxide is increased, especially chronic or repeatedly, three vicious biochemical cycles can then be set in motion. These cycles are labeled as 1, 2, and 3 in the chemical diagram on page 9.

    1. Excess Peroxynitrite Vicious Cycle

      Nitric oxide forms a tissue damaging free radical known as peroxynitrite.3. This then forms even more nitric oxide.

      Peroxynitrite is a highly potent free radical that damages proteins (including enzymes), lipids (brain and cell walls, mitochondrial (energy producing) membranes, ribosomal  (protein making) membranes and genetic (DNA) membranes.

      Antioxidants such as natural Vitamin E (tocopherols) and related substances called tocotrienols (act like vitamin E in brain and lipid membranes), vitamin C (ascorbic acid), and glutathione help protect against these effects.9 The body needs selenium and vitamin B2 to help glutathione function well to help heal damage.9

      This vicious cycle with increased nitric oxide and peroxynitrite can cause brain cell death and neurogenerative disease.3,8,19

      Peroxynitrite also weakens the blood-brain barrier, allowing chemicals to enter the brain more readily.  Nitric oxide also damages the first detoxification step, allowing chemicals (and many drugs) to build up more in the body. This further increases inflammation.

      The body has a natural enzyme to help protect from this damage. It is called SOD (superoxide dismutase). It needs certain minerals to help it function (zinc, copper and manganese).

      Exhaled nitric oxide is a medically accepted marker of airway inflammation.

    2. Excess Superoxide Vicious Cycle

      Peroxynitrite forms damaging superoxide free radical, which then further increases nitric oxide. Superoxide is a damaging free radical that also causes the damages discussed above for peroxynitrite.

    3. Damage to Mitochondria/Energy Structures

      This damage increase NMDA, which further increases Nitric Oxide

      Peroxynitrite depletes energy ATP, which then further increases the sensitization of NMDA. ,   Increased peroxynitrite forms excess hydroxyl radical, which in turn damages energy-making).

      Mitochondria are structures in body cells that generate energy by producing ATP. Mitochondria damage has been documented in the vast majority of patients with chronic illness from chemical injury.  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.   Healing substances are needed to help these body protections function better.

      Neural sensitization thus involves self-perpetuating excess brain/nerve cell (neuroexcitation) response to further chemical exposure.25 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.

      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.   Healing substances are needed to help these body protections function better.

      Neural sensitization thus involves self-perpetuating excess brain/nerve cell (neuroexcitation) response to further chemical exposure.25 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.