Martin Pall, PhD, professor emeritus of biochemistry and basic medical sciences at Washington State University, has posted a groundbreaking article on the mechanisms of MCS - “Multiple Chemical Sensitivity: Toxicological and Sensitivity Mechanisms” - on his website (TheTenthParadigm.org). This is a condensed version of a longer article which will be published in the third edition of General and Applied Toxicology – a prestigious reference book on the latest science in this field, due out in December. The condensed version will soon be translated into German, French, Spanish, and Italian.
Discounts the “Psychogenic” Theory of MCS
By linking MCS to specific genes associated with susceptibility, specific chemical stressors, and chronic symptoms they may initiate via the NO/ONOO- cycle,* Dr. Pall explains many of the disorder’s previously unexplained properties – while discounting the “psychogenic” theory of MCS. He concludes by identifying five key areas for further research.
Abstract Summary of the Article:
Multiple Chemical Sensitivity: Toxicological and Sensitivity Mechanisms
(To read the full article, click here.)
Cases of multiple chemical sensitivity (MCS) are reported to be initiated by seven classes of chemicals. Each of the seven acts along a specific pathway, indirectly producing increases in NMDA activity in the mammalian body. [NMDA is an "excitotoxin" - a substance that causes nerve cell damage.]
Members of each of these seven classes have their toxicant responses lowered by NMDA antagonists, showing that the NMDA response is important for the toxic actions of these chemicals.
The role of these chemicals acting as toxicants in initiating cases of MCS has been confirmed by genetic evidence showing that six genes that influence the metabolism of these chemicals all influence susceptibility to MCS. It is likely that chemicals act along these same pathways, leading to increased NMDA activity when they trigger sensitivity responses in MCS patients.
The chronic nature of MCS and also related multisystem illnesses is thought to be produced by a biochemical vicious cycle mechanism, the NO/ONOO- cycle, which is initiated by various stressors that increase nitric oxide and peroxynitrite levels (with some but not others acting via NMDA stimulation).
The NO/ONOO- cycle is based on well documented individual mechanisms. The interaction of this cycle with previously documented MCS mechanisms, notably neural sensitization and neurogenic inflammation, explains many of the previously unexplained properties of MCS.
This overall mechanism is also supported by:
• Physiological correlates found in MCS and related multisystem illnesses,
• Objectively measurable responses to low level chemical exposure in MCS patients,
• Many studies of apparent animal models of MCS,
• And also evidence from therapeutic trials of MCS-related illnesses.
Some have argued that MCS is a psychogenic illness, but this view is completely inconsistent with this diverse data on MCS and related illnesses, and the literature claiming psychogenesis of MCS is deeply flawed. In addition, two rare predictions that can be used to test psychogenesis both lead to rejection of the psychogenic hypothesis.
While the NO/ONOO- cycle mechanism for MCS is supported by many different observations, there are also multiple areas where further study is needed.
Martin L. Pall, PhD
• Professor Emeritus of Biochemistry and Basic Medical Sciences, Washington State University
• Research Director, Tenth Paradigm Research Group, Portland, Oregon
* See also:
"Nitric Oxide Cycle Theory: Will it Explain CFS, FM, and Other 'Unexplained' Illnesses? - Q&A with Martin L. Pall, PhD"