June 15, 2017

The Proposed Mechanism for Multiple (body system) Chemical Sensitivity

It's popularly known as Multiple Chemical  Sensitivity (aka MCS.)
However, the diagnostic title does NOT refer to the phenomenon of
sensitivity to multiple chemicals.  It refers to chemical sensitivity
simultaneously afflicting multiple body systems, and not merely
one of them.

Concerning sensitivity to multiple chemicals, that phenomenon had long
since been proven to be real in cases of asthma, sinusitis, rhinitis, vocal
cord dysfunction, dermatitis, and a medical condition known as Reactive
Airways Dysfunction Syndrome.

The 21st Century's 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 activation
(action potential.)

Specific chemoreceptors, upon their activation, elevate nitric oxide levels
in the body.  The nitric oxide reacts with superoxide, producing peroxy-
nitrite.

While the nitric oxide is engaged in producing peroxynitrite, it is simul-
taneously engaged in an additional function.  This function is "retrograde
signaling."

Nitric oxide's role in retrograde signaling is proposed to be that of send-
ing an electrical signal to the presynapse cells, thereby stimulating the re-
lease 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.  Abbreviat-
ted "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 maintain an elevated nitric oxide level, per-
oxynitrite is engaged in causing the cells that contain those receptors to
be depleted of their energy pools.  Adenosine triphosphate is what's be-
ing depleted in the process.  Now, ATP is the carrier of energy in all liv-
ing organisms, and peroxynitrite inhibits mitochondrial function.  There-
for, it inhibits the production of ATP.

When cells containing NMDA receptors become deprived of their ener-
gy pool's replenishment, the NMDA receptors become hypersensitive to
stimulation.  And while the cells containing NMDA receptors are being
deprived of energy replenishment, peroxynitrite is engaged in yet another
process; that of  breaking down the blood brain barrier.  This enables in-
creased chemical access to the brain.

Meanwhile, nitric oxide performs yet another function; that of  inhibit-
ing cytochrome P450 activity.  Therefore, nitric oxide is proposed to
inhibit the process by which chemicals get metabolized and become
harmless.  The result is heightened sensitivity to chemical exposure.

The aforementioned scenario was proposed by Dr. Martin L. Pall, of
the School of  Molecular Biosciences of  Washington State.  The afore-
mentioned scenario is called "a vicious cycle mechanism"  and a paper
written by Dr. Pall which describes this vicious cycle.

http://www.allergyresearchgroup.com/Explaining-by-Martin-Pall-PhD-sp-35.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 Drs. Pall and Julius Ander-
son, M.D., Ph.D., of West Hartford, Vermont;   The Vanilloid Re-
ceptor as the Putative Target of Diverse Chemicals 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 activa-
tion is proposed to be the point where the vicious cycle begins.  The
vanilloid receptor paper also addresses the phenomenon of  masking,
a phenomenon duly noted in Central Chemical Sensitivity. 

    The Phenomenon of Masking is actually Dephosphorylation

Masking is the phenomenon where a chemical exposure scenario gets
muted at the outset by the overshadowing effect of  a previous and dif-
ferent one.  That same chemical exposure would have resulted in a not-
able adverse reaction if  it were the first one of that day.  The same ex-
posure will result in an adverse reaction when it becomes the first one,
on some future day.  The masking effect muted the presence of  that
specific chemical exposure for that particular day.

Masking is liken to drinking scalding coffee.  After having done so, ev-
en 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 inability 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's a phase triggered
by Ca2+ calmodulin phosphatease calcineurin.  Vanilloid receptor activity
is decreased during that phase; the "desensitization" phase.  Conversely,
it is during the alternate phase, the one known as phosphorylation, when
vanilloid receptor 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 pub-
lished in the August/September 2005 edition of  Townsend Letter for
Doctors and Patients.  It can be accessed by clicking on the following
web address:

http://academic.research.microsoft.com/Paper/6500302

Now, the proposed mechanism of Dr. Pall is a hypothesis.  It is a hypo-
thesis which involves intricate details and intricate mapping.  This means
that the objective medical findings of chemically sensitive patients contin-
ue to carry the sole weight in proving that chemical sensitivity is a physi-
ological condition and not a psychiatric one.

The objective medical findings include instances of  anaphylaxis triggered
by nontoxic/ambient/therapeutic levels of  chemical-bearing agents.  The
findings include cases where two entirely different species of  localized
chemical sensitivity were found co-existing in the same one patient, and
such co-existence hints of the authentic existence of  MCS. 

Peripheral Chemical Sensitivity

This general type of chemical sensitivity is proposed to involve the per-
ipheral 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, as is Occupational Asth-
ma due to low-weight molecular agents..

This type of chemical sensitivity is proposed to involve neurogenic in
flammation.  One can obtain more information on this type of chemi-
cal 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 Sensi-

tivity to Environmental Chemicals.

http://www.herc.org/news/mcsarticles/meggs-full.html
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