Martin L. Pall, Professor Emeritus of Biochemistry and Basic Medical Sciences at Washington State University has developed a unified theory to explain the common etiology and mechanism underlying  chronic fatigue syndrome, multiple chemical sensitivity, fibromyalgia, and post-traumatic stress disorder.  Pall tells us that these four multi-system illnesses often occur together in the same individual and share many of the same symptoms.  He says that Gulf War Syndrome is a fifth illness that is a combination of the four.

Pall outlines 17 physiological stressors that are known to initiate one or more of these illnesses, all of which have in common the fact that they can elevate nitric oxide levels or stimulate a process that does so.

He goes on to explain how elevated levels of nitric oxide can cause chronic illness by saying,

“…nitric oxide, acting primarily through its oxidant product peroxynitrite, initiates a biochemical vicious cycle that is responsible, in turn, for the chronic illness.  We have, then, an initial cause of illness (short-term stressor or stressors) acting to start this vicious cycle, with the cycle responsible for causing the chronic phase of illness.  We are now calling the cycle the NO/ONOO- cycle after the structures of nitric oxide (NO) and peroxynitrite (ONOO-) but pronounced no, oh no!”

Five principles underlying the NO/ONOO- cycle as an explanatory model
Pall has identified five principles underlying the NO/ONOO- cycle as an explanatory model,

1.  Short-term stressors that initiate cases of multisystem illnesses act by raising nitric oxide synthesis and consequent levels of nitric oxide and/or other cycle elements.

2.  Initiation is converted into a chronic illness through the action of vicious cycle mechanisms, through which chronic elevation of nitric oxide and peroxynitrite and other cycle elements is produced and maintained.  This principle predicts that the various elements of the NO/ONOO- cycle will be elevated in the chronic phase of illness.

3.    Symptoms and signs of these illnesses are generated by elevated levels of nitric oxide and/or other important consequences of the proposed mechanism, i.e. elevated levels of peroxynitrite or inflammatory cytokines, oxidative stress and elevated NMDA and vanilloid receptor activity.

4.    Because the compounds involved, nitric oxide, superoxide and peroxynitrite have quite limited diffusion distances in biological tissues and because the mechanisms involved in the cycle act at the level of individual cells, the fundamental mechanisms are local. The consequences of this primarily local mechanism show up in the multisystem illnesses through the stunning variations one sees in symptoms and signs from one patient to another.  Different tissue impact of the NO/ONOO- cycle mechanism is predicted to lead to exactly such variations in symptoms and signs.  One also sees evidence for this fourth principle in published brain scan studies where one can directly visualize the variable tissue distribution in the brains of patients suffering from one of these illnesses.

5.    Therapy should focus on down-regulating the NO/ONOO- cycle biochemistry.  In other words, we should be treating the cause, not just the symptoms.

Therapeutic protocol

Fourteen other illnesses may also fall under this new disease paradigm.  Various therapeutic protocols designed to down-regulate NO/ONOO- cycle biochemistry are also presented at The Tenth Paradigm, in addition to a full web page on the NO/ONOO- cycle mechanism relation to FMS, CFS/ME, and MCS.  Although the recommended therapeutic protocols are not a cure, anecdotal evidence indicates improvement for those who are able to tolerate the recommended substances.

While this might all sound like scientific mumbo jumbo, especially when we are struck by brain fog, in my opinion and my observations related to my own illness and its multiple interconnections, Pall’s unified theory is a very promising explanation.

We are extremely fortunate to have a scientist like Pall so dedicated to understanding the causes and treatment options for these disorders.  I find it exciting to look ahead and see that in ten years’ time there will likely be a full understanding of these disorders.

The whole notion that these illnesses are psychogenic in origin is passé, but it can take 10 years time for research to be validated and integrated into clinical medicine.  Our doctors may not be aware of the current research for many years. We can help educate them by offering the link to The Tenth Paradigm’s scientific explanation.  Pall is also author of the book Explaining Unexplained Illnesses.

This and other proposed scientific theories on the etiology of multiple chemical sensitivity in particular are synopsized at the James Madison University MCS website.

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