The 21st Century proposed mechanism for MCS identifies two general
categories of chemical sensitivity. They are Central Chemical Sensitiv-
ity and Peripheral Chemical Sensitivity. The outline goes as follows:
Central Chemical Sensitivity
This type of chemical sensitivity involves the central nervous system,
and it's triggering point is proposed to be found in chemoreceptor ac-
tivation (action potential.)
Specific chemoreceptors, upon their activation, elevate nitric oxide
levels in the body. The nitric oxide reacts with superoxide, produc-
ing peroxynitrite.
While the nitric oxide is engaged in producing peroxynitrite, it is si-
multaneously engaged in an additional function. That function is
"retrograde signaling."
Nitric oxide's role in retrograde signaling is proposed to be that of
sending an electrical signal to the presynapse cells, thereby stimu-
lating the release of two types of neurotransmitters. The two types
are glutamate and aspartate.
Those types of neurotransmitters then stimulate receptors in the post
synaptic cells, known as N-methyl-d-aspartate receptors. Abbrevi-
ated "NMDA receptors", they react by producing nitric oxide from
their own sites, thereby maintaining the inordinately high level of
nitric oxide already present. Nitric oxide's ample presence proceeds
to maintain the inordinately high levels of peroxynitrite.
While the NMDA receptors are maintaining an elevated nitric oxide
level, peroxynitrite is engaged in causing the cells that contain those
receptors to be depleted of their energy pools. That which is being
depleted is adenosine triphosphate (ATP), the carrier of energy in
all living organisms. Peroxynitrite inhibits mitochondrial function,
and therefore, the production of ATP.
When cells containing NMDA receptors become deprived of their
energy pool's replenishment, the NMDA receptors become hyper-
sensitive to stimulation. And while the cells containing NMDA re-
ceptors are being deprived of energy replenishment, peroxynitrite
is engaged in yet another process; that of breaking down the blood
brain barrier. This enables increased chemical access to the brain.
Meanwhile, nitric oxide performs yet another function; that of in-
hibiting cytochrome P450 activity. Therefore, nitric oxide is pro-
posed to inhibit the process by which chemicals get metabolized
and become harmless. The result is heightened sensitivity to chem-
ical exposure.
The aforementioned scenario was proposed by Dr. Martin L. Pall,
of the School of Molecular Biosciences of Washington State. The
aforementioned scenario is called "a vicious cycle mechanism" and
a paper written by Dr. Pall which describes this vicious cycle can be
accessed by clicking on the following web address:
http://ehp.niehs.nih.gov/realfiles/members/2003/5935/5935.html
Vanilloid Receptor TRPV1
Recently added to this proposed mechanism is the first member of
the Vanilloid Receptor family, TRPV1. The involvement of TRPV1
in MCS is the subject of a paper written by Dr. Pall and a Dr. Julius
Anderson, M.D., Ph.D., of West Hartford, Vermont. It is titled,
The Vanilloid Receptor as the Putative Target of Diverse Chemi-
cals in Multple Chemical Sensitivity. The bibliographical citation
for it is Arch Environ Health. 2004 Jul;59(7):363-75.
The vanilloid receptor is implicated as a major target for a number
of chemicals which can activate it. Therefore, vanilloid receptor
activation is proposed to be the point where the vicious cycle be-
gins. The vanilloid receptor paper also addresses the phenomenon
of masking, a phenomenon duly noted in Central Chemical Sensi-
tivity.
Masking is the phenomenon where a chemical exposure scenario
gets muted at the outset by the overshadowing effect of a previous
and different one. That same chemical exposure would have re-
sulted in a notable adverse reaction if it were the first one of that
day. That same chemical exposure will result in an adverse reac-
tion when it becomes the first one, on some future day. The mask-
ingeffect muted the presence of that specific chemical exposure
encounter for that particular day.
Masking is liken to drinking scalding coffee. After having done so,
even cold water gives a scalding effect. Yet, if the cold water were
taken before the scalding coffee, it would have no ill effect. Thus,
after having been exposed to one incitant (trigger), there is an inabil-
ity to differentiate between things to which you are hyper-reactive
and things to which you are not.
The authors of the vanilloid receptor paper propose that masking
occurs during a cyclic phase known as dephosphorylation. It is a
phase triggered by Ca2+ calmodulin phosphatease calcineurin. The
hypothesis is that vanilloid receptor activity is decreased during that
phase; the "desensitization" phase. Conversely, it is during the alter-
nate phase, the one known as phosphorylation, when vanilloid re-
ceptor activity increases, and hypersensitivity reactions resume.
Therefore, the phosphorylation state determines the activity or
inactivity (desensitization) of the vanilloid receptors.
In addition to the paper that Martin Pall co-authored, there is an
article on the vanilloid receptor that he individually authored. Titled,
Multiple Chemical Sensitivity: towards the end of controversy. It
was published in in the August/September 2005 edition of Town-
send Letter for Doctors and Patients. It can be accessed by clicking
on the following web address:
http://www.findarticles.com/p/articles/mi_m0ISW/is_265-266/ai_n15688810/pg_3
The article cannot be regarded as a substitute for the recent paper
on TRPV1. But, it does provide enough information to enable a
reader to become familiarized with the recently added feature of
Dr. Pall's proposed mechanism for MCS.
Now, the proposed mechanism of Dr. Pall is a hypothesis. It is
a hypothesis which involves intricate details and intricate mapping.
This means that the objective medical findings of chemically sensi-
tive patients continue to carry the sole weight in proving that chem-
ical sensitivity is a physiological condition and not a psychiatric one.
The objective medical findings include instances of anaphylaxis
triggered by nontoxic/ambient/therapeutic levels of chemical-bear-
ing agents. The findings include cases where two entirely different
forms of localized chemical sensitivity were found co-existing in the
same one patient. Such co-existence hints of the authentic existence
of MCS.
Peripheral Chemical Sensitivity
This general type of chemical sensitivity is proposed to involve the
peripheral tissues. Reactive Airways Dysfunction Syndrome is
placed in this category, as is Reactive Upper-airways Dysfunction
Syndrome. The contact sensitivity conditions, such as Airborne
Irritant Contact Dermatitis, are also placed in this category.
This type of chemical sensitivity is proposed to involve neurogenic
inflammation. One can obtain more information on this type of chem-
ical sensitivity by clicking on the following links:
Hypothesis for Induction and Propagation of
Chemical Sensitivity Based on Biopsy Studies.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469810/
Neurogenic Inflammation and Sensitivity to Environmental Chemicals.
http://www.herc.org/news/mcsarticles/meggs-full.html
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