Martin L. Pall
Professor Emeritus of Biochemistry and Basic Medical Sciences, Washington
State University and Research Director, The Tenth Paradigm Research Group
638 NE 41st Ave.
Portland, OR 97232-3312 USA
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.
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 2
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.
Key Words: Peroxynitrite; oxidative stress; excitotoxicity; mitochondrial
dysfunction; long term potentiation; chronic fatigue syndrome/myalgic