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A new model about the origin of chronic pain

A complete new insight in the origin of chronic pain and CRPS

After the Gate Control Theory (1965 by Ronald Melzack and Patrick Wall) structural ideas about the origin of chronic pain has been failed to appear. This Blog wil try to give an alternative idea about the origin of chronic pain and CRPS as parts of the same disease. Disease indeed, not a syndrome. There is a measurable beginning, a measurable and influenceable course and cure to some extent.

Hypothesis: An aetiological model of chronicpain and CRPS : Phases of the same inflammatory condition
This blog will follow the whole article with the same name with many explanations. An officially published article needs shortness. In this case it requires a broad professional knowledge of different medical specialisms too. This kind of knowledge is apparent very seldom. Super-specialists don't have sufficient insight in the knowledge of other super-specialists. And that's the real problem of chronic pain. It is clear that the explanation of the origin of chronic pain cannot be short. This Blog will be added, adjusted with new content and adapted to questions received.

Therapeutic possibilities

therapeutic possibilities Posted on Mon, September 03, 2018 15:03:48

Post 17
The final post about the new model of chronic pain.

Existing and new therapeutic
possibilities according to the new model.
Both for chronic pain and CRPS there are theoretically possibilities based
on rationally medical insights. Some of them are used in practice already.
However the tradition of trial and error is still applied in most cases, not
bothered by scientifically arguments. Even if that is not necessary.

First of all chronic pain will be discussed, simply because the author has been
started with that 45 years ago and because chronic pain in the new model is considered
as the possible precursor of active
CRPS. Handling of chronic pain therefore means a prophylactic approach of CRPS
at the same time. The fundamental idea of treatment in the context of the new
model is the argumentation, that a
bleeding, fracture or operation always is followed by an inflammatory process.
Required for a normal recovery process.
However not every patient is recovering completely. It is a complex
event in which prostaglandins are playing an essentially role. That are very
unstable molecules, much more than the peptide molecules with which they have
been combined. (And have to combine vice versa).
The peptides, called cytokines, exist in two kinds: activating or inhibiting inflammatory
processes. There is a relationship between
prostaglandins and pain. Pain is an accompanying phenomenon in case of tissue
damage. The signal of it is actual and normally temporary if the tissue has
been repaired. However people, who don’t have pain sensation at all, have a fast
degeneration of the joints. The mechanism for that is unclear and it doesn’t
mean that pain stimulates tissue repair. It is more likely, that the same
mechanisms in which pain has been involved
are influencing tissue repair too.
So far this shortly summary , needed for understanding the art of pain
Pain has been treated with medicines since the beginning of the 20th
century already. With anaesthetics like alcohol and opium probably centuries
earlier. A drug like aspirin has been developed because willow bast had been
used as a local treatment of pain and inflammation of the skin. The
biologically active principle was salicylic acid. But that turned out to be too
harming for the stomach wall. Coupled to acetic acid the drug had been much
safer. The aspirin had been born.
Another painkiller had been found as a result of aniline research. A
derivative, named as Novaminsulfon showed itself to have painkilling
properties. Both aspirin and novaminsulfon are used to date as the most
important pain inhibiting pharmaceuticals in the world.
Today we know, they are working by inhibiting the prostaglandin synthesis from
cholesterol. Pain is inhibited by decrease of the prostaglandin concentration.
Besides the peripherally prostaglandin synthesis from cholesterol there is
another and also important way to produce the prostaglandins. Release from the
cell wall itself. This way of production is regulated by adrenocortical steroid
hormones like prednisone.
But not only by inhibition of the prostaglandin concentration pain can be
diminished. Also by blocking of their activity. Drugs like cocaine, morphine
and other such have such properties.
They have the capacity to penetrate the blood-brain barrier and reach the
central nervous system.
Therefore they are called central analgesics in contrast to the prostaglandin
synthesis inhibitors, which are called peripheral analgesics.
A special group has cocaine as starting point. In the French-German war at the
end of the 19th century there was an important need for local
anaesthetics. Besides the local anaesthetic action on the eye, cocaine showed a
proved local effect after injection. But the side effects had been unwanted. In
the first decades of the 20th century scientifically research had
been resulted in a new local anaesthetic named procaine. At today procaine is
used in a special branch of complementary medicine, developed in Germany and known
as Neural therapy. Succeeding local anaesthetics with lidocaine as an important
representative are used in the medical practice today.
For chronic pain treatment ” Neural therapy” is very effective. The local
anaesthetics have been proven prostaglandin agonists and antagonists.
Nowadays electronic equipment and surgical methods have been used to diminish
pain too, but these techniques are out of the scope of this pain model. That is
a biochemically model and the possibilities for treatment will be concerned
within this model. So pharmacologically.
Besides the drugs acting on the behaviour of prostaglandins there exist another
element for influencing pain, not yet implemented in the medical practice: the
buddy-coupling element of prostaglandins to cytokines.
Medically intention is pointed to the prostaglandins or the cytokines,
dependent of the interest in pain or inflammation. But in reality
prostaglandins and cytokines are working together in pain and inflammation. So
you can expect that blocking of cytokines is resulting in decreasing of pain
too. In the eighties of the 20th century prostaglandins had been a
well-known research item, but cytokines not or scarcely. Still then had been
started a research-project with a cytokine-blocker in case of chronic pain,
without the knowledge about that pharmacologically aspect.
The idea behind the research project had
been evolved from the findings, that chronic pain is generated in the SKIN and
the phenomenon of vasoconstriction in 75% of the areas with chronic pain. We
expected, that vasoconstriction and the resulting lack of oxygenation might be
the spring of pain generation. Only in 1986 we had to our disposal accurately
measurement equipment and a new pharmaceutical for better perfusion of narrowed
vessels. And indeed, it had been worked. Pain decreased and the skin had been
perfused left and right sided symmetrically.
Only recently in the 21th
century the underlying biochemical details has been known.
The drug : pentoxifylline (PTX) sold as Trental® is acting like
a phosphodiesterase inhibitor and is blocking some specific cytokines. Result: vasodilation and blocking
of inflammation.
These cytokines are produced in high
quantity in case of traumas, inflammations, fractures and (orthopaedic) operations. In most cases they are
disappearing when recovery has been finished. That is normal, because they have
a function in tissue repairing.
But it seems, that the recovery in some people has not been completely. The
activity of Trental® is looking suspicious for a cold
chronic form of inflammation in the scar area, even if the naked eye cannot see
a scar. But infrared thermography is able to measure it.
Due to the combined properties of pentoxifylline it looks as the first choice
pharmaceutical in case of chronic pain. More suitable than the blocking agents
of the prostaglandin synthesis only , not addictive or habit-forming like
oxycodone and much more cheaper than modern biologicals as infliximab. It is
amazing that it has not been used yet.

It is much easier to see CRPS as a disease than to do the same with chronic pain.
Chronic pain has to be rid of his psychologically phantom first. Besides CRPS
has been investigated thoroughly already.
Therefore it is amazing, that the results of all these investigations did not
have resulted into practically treatment. In the case of CRPS many cytokines
had been produced and analysed. Cytokines as described above. Together with
their prostaglandin buddies they are causing a severe inflammation, without
hardly negative feedback possibilities. The huge amount of prostaglandins are
locally produced from cholesterol and cell wall elements. Neither the cell wall
prostaglandins, nor the cytokines are blocked by the usually techniques. Still
there have to be possibilities to handle CRPS with pharmaceuticals, blocking
the cytokines. One patient has been cured in Rotterdam with a modern biological
(infliximab) and described as a case report. The extremely high costs of that
biological is discouraging further investigation impossible. But as described
above there exists another old and cheap pharmacological, which has the
possibilities to block the same cytokines as infliximab. Contrary to infliximab
(€ 19000 a year) Trental® costs about € 250 a year.
Today it is used for blocking TNF-alfa only in experiments with animals.
But Trental® is a normally registered
pharmaceutical for better perfusion of the vessels.
The Erasmus university is possessing a fully followed and described case of
CRPS, treated with Infliximab. I have a fully followed and described case of
CRPS, treated with Trental®. Both patients are cured. So where
is the blockade for further investigation?

Prevention of CRPS is an important matter. Even more it is possible on an easy
In the model chronic pain can result in CRPS with small traumas or by
stimulation of the autonomic nervous system. In case of trauma it is looking
logically: much cytokines have been produced in the body tissue. However, what
is the role of the central nervous system?
That is to investigate with testing.
With cold stress alone the infrared measured values in CRPS have been worsened.
After taking a test dose PTX (Trental®) the infrared values with cold stress are nearly normal.
That is suggesting a stimulating effect of the autonomous nervous system on
activating CRPS by activating the cytokines.
As a consequence of that patients with a CRPS risk, namely those pain patients
with a temperature increase after cold stress, can be expected to have a profit
in using Trental® in risky situations.
Risky situations are elite sport and planned non-deferrable operations in a
pain area. That is a rationally directed therapy as a prevention of a worsening
case. It is possible. The possibilities exist more than thirty years already, but
are not used yet.

It is pity.

Henk van der Veen 09-09-2018

Diagnostic findings in a new model

diagnostic possibilities Posted on Fri, August 24, 2018 16:59:11

Post 16

Diagnostic findings with infrared thermography, in relation to a new model of
chronic pain
Normally it is wise to explain a model before presenting it. However I have
made the choice to do that afterwards, because a model is an abstraction too.
It is easier to concretise by an explanation after the presentation.

Summary of the previous posts.

{From the skin vasodilation can be measured by temperature increase and
vasoconstriction by temperature decrease. The model has as fundamental idea
that the skin is responsible for generating the experience of chronic pain.
Chronic pain is disappearing temporarily (sometimes longer) after local
anaesthesia of the area of pain in the skin. Local anaesthetics are blocking
prostaglandins and prostaglandins have vasoactive effects. Those effects are
measurable by infrared thermography.}
Different findings have been showed, which are looking to conflict with
each other.
Some of them are appearing to interfere with a scientifically explanation. That
is the same contradiction scientists
have been found in a new group of biochemically active compounds in the
sixties and seventies of the past century. The group of prostaglandins.
Thousands of scientifically papers have appeared, but the results are very
contradictory. But finally everybody have found each other in some crucially
conclusions: Prostaglandins alone do not have any biologically effects! Only
functioning as a buddy together with another biologically active compound they
modulate and regulate that function. They have a role in muscle activity, blood
vessel perfusion, pain, inflammation, activity of nerve cells and nerve fibres
and hormonal activity.
One can find them anywhere in the body. They are originated and destructed locally.
Their biological half live is very short. If they passed into the blood
circulation they have been disappeared within one passage. Because they don’t
have a biologically effect alone, but only modulate and regulate effects of
other biologically active compounds, they are called locally hormones.
In relation with the phenomenon of chronic pain their effects in originating
pain, inflammations and activating or inhibition of the activity of the nervous
system have an extraordinarily significance.
Nothing produces nothing. Also pain doesn’t appear from nothing. Pain is an
actually signal. There is something happening! For chronic pain especially
inflammation is an important element.
Every trauma of the human tissue is originating an inflammation. Mostly
temporarily. Inflammation is a normal
and essential side-effect in wound-healing. Prostaglandins are the leading
factors for a normal course of that process.
A memory of pain seems not to exist. It is difficult to quantify formerly pain,
if the pain has been leaved. That is pointing to an actual temporary pain
In 1977 some papers are published about the activity of a range of prostaglandins,
which could be produced synthetically. The results of in vitro research with muscle
preparations. Only in such a situation is reliable research with low doses of prostaglandins
possible. For that it is necessary to shut down the whole physiologically prostaglandin
synthesis in the preparation. Therefore is used indomethacin as blocking agent
mostly. Indomethacin is a drug, which is used in living humans for inhibition
of inflammation or pain too. It is clear, that a complete shut-down of the
body’s own prostaglandin synthesis is not possible in living humans. The human
is dead then.
So there is always interfering with physiologically produced prostaglandins.
The physiologically concentrations are lying between femtograms and picograms
per millilitre body tissue fluid. (one millionth of a billionth per millilitre
till one millionth of a millionth per millilitre).
And just that can explain the differences between the found results.

It is a strange matter the way
of thinking about a linear dose-effect relationship in the area of
pharmacology. It means that the effect
has been supposed to be doubled, when the concentration has been doubled etcetera,

However the
reality for many biochemically active compounds is not a straight line, but a
bell shaped curve in most situations.

difference is clear. Above a certainly concentration (“B”) the effect do not
increase anymore, but decreases. Moreover the effect changes reversely above a
higher concentration.
In this example the effect changes from vasoconstriction into vasodilation.
Horrobin and Manku had demonstrated this
definitely in 1977 already.

The modification of their results has been demonstrated in this Blog earlier.

The X-axis represents the concentration of prostaglandins in a logarithmically
scale. A: zero and C: 100 ng/ml. The Y-axis shows the effect: vasoconstriction
or vasodilation. The concentration level of 100 ng/nl forms the switch.
Some different types of prostaglandins are known with the same parabolic curve.
Two types are important in this model : Prostaglandin E (PGE) and prostaglandin
F (PGF). According the results of Horrobin and Manku PGE is acting like a
vasoconstrictor in low dose and PGF as a vasodilator.
The own physiologically prostaglandin production in their preparation had be
set on zero first.
However it is remarkable that most researchers are reporting a stimulating
effect on inflammation with vasodilation of PGE. The contrary is reported about
Reviewing the papers with these results shows that most of these results have
been reached with existing levels of physiological prostaglandins as a base.
The conclusion must be that in most cases not low (physiologically) levels have
been measured, but levels above 100 ng/ml, therefore after the switch. In the
model we shall see the significance of that in different options. We can
measuring that with infrared thermography in specific physiologically test
Because PGE and PGF are counteracting each other a resulting action exists.
In this model is showed the action of PGE as “E” and the action of PGF as “F”.
In formerly versions of the model the Y-axis seems to represent
vasoconstriction. That’s confusing with showing the levels of effect both of
PGF as PGE. They are counteracting.
It is better to show the Y-axis as a level of action. If E>F the result is
vasoconstriction. If F>E the result is vasodilation.

In a
healthy physiologically situation the vasoactive properties of the
prostaglandins are measurable with infrared thermography. That is useful for
measurements of physically exercise par example, but infrared thermography is
useful for testing of diseases or prevention too. Especially in case of chronic
pain and CRPS. Then it is the first choice.
There is one method for producing prostaglandins in the human body without
tissue damaging. It is called “Cold Stress”. A part of the body is cooled down
by a cooling body pack. During the cooling down procedure the orthosympathetic
part of the autonomous nervous system is stimulated. By the resulting
prostaglandin “E” (PGE) is the normal reaction in a healthy person:
vasoconstriction. The skin temperature decreases, not only within the body
pack, but over the whole body surface. That is the result of an autonomous
reflex. There are more easier and cheaper ways to do this: Within the
thermographically departments of medicine Cold Stress is generated by cooling
down feet or arms into a footwell with water of 19 degrees Celsius during ten
minutes. That is sufficient. In generally it is possible to make ten
measurements: every minute one. It delivers a lot of information. Cheap, safely
and harmless.
With cold stress there are six possibilities to study:

1. Cold skin areas are colder
2. Warm skin areas are colder
3. Cold skin areas are warmer
4. Warm areas are warmer
5. Threatening CRPS
6. Beginning CRPS

Active CRPS doesn’t need testing. Diagnosis by questionnaires and a “hot
picture” is sufficient. Cold stress will damage the tissue by activating the
Temperature decrease during the test is a normal physiologically reaction, but
an increase is always pathological. The old term for CRPS is “Autonomic reflex
However temperature increase by Cold Stress is normally not comprehendible. May
be that is a reason to change the term of “Autonomic reflex dystrophy” into
That discrepancy forms the base of the model: Chronic pain and CRPS are NOT
different diseases, but only different PHASES from the same disease. You can
see it in the figure above.

Back to the possibilities.

Cold skin areas are colder

In this
model a cold painful skin area means a resulting PGE effect. PGE-PGF>0
The effect has been plotted on the Y-axis. So point E must be higher on the
Y-axis than point F.
Point E has two theoretically places:
High on the ascending leg of the curve or high on the descending leg. (E or
EX). EX cannot be the place, because by cold stress the prostaglandin
concentration increases and therefore EX falls to the X-axis. The difference
between EX and F becomes smaller and the temperature increases. But we measured
a temperature decrease.
Therefore is E the right place. It has to be between concentrations of 500 and
1000 picogram (1000 picogram=1 nanogram) per millilitre. F has to be between 10 and 100 nanogram per millilitre. With
increasing prostaglandin (PGE) concentration there is a shift toward point B. The
difference between E and F increases and the temperature decreases. And just
that we are measuring.

Warm skin areas are colder
That’s a normal situation in the recovery stage of an inflammation.

In fact
this is a physiologically situation. It represents an compensating balance
between PGE and PGF with the possibility to give negative feedback, a normal condition
for every stable measuring and regulation system. F has
to be high on the curve, above the level of E.
There has to be a positive result between F and E. (F-E>0). The
physiological result is vasodilation and a warm skin area. Point E cannot be on
the descending leg of the curve, because the risk to provoke a CRPS. That would
be a dangerous situation instead of a physiologically process. (see: warm areas
are warmer).

Cold skin areas are warmer.

The first image in the measuring process is showing a cold skin area. Therefore
point E has to be higher on the curve than point F. Point E cannot be on the
ascending leg: with cold stress the concentration increases and the
vasoconstriction too. The only possible place is high on the descending leg. (Point
EX). With increasing concentration PGE the effect decreases and
vasoconstriction is diminishing then. The result is vasodilation and a skin
temperature, which is increasing.
By some researchers this situation is called CRPS too, but probably the CRPS
questionnaires are still negative. In fact it is a risky phase in originating
CRPS. These patients should not to be operated trying to cure them from their pain.
Active CRPS can be expected.
Another group of patients should not be operated due to their pain too. The CRPS
risk is even more higher.

Warm pain areas are warmer
Point E is located with a high concentration PGE nearby point C.

The area is
warm. Point F has to be located high on the descending leg of the curve. Vasodilation
predominates. Theoretically should it be possible that Point F and point E are
to be located on the ascending leg of the curve, but that is a physiologically
situation. The concentrations of PGF and PGE are too low for producing pain
then. Only F can be located high on the ascending leg, but it is unlikely that
such a low concentration of PGF can be combined with a high concentration PGE.
A physiological situation at one hand and a pathological at the other together….
That is not a logically combination.
Anyway the result is vasodilation and the temperature of the pain zone increases.
There is an high risk for CRPS:
The increasing concentration PGE by cold stress can pass Point C (100ng/ml) and
then PGE becomes vasodilatative and inflammatory properties enhanced by the
intrinsic properties of PGF.
There is a positive feedback and CRPS is starting.
Therefore this situation is classified by some researchers as CRPS too, but
there are possibilities for negative feedback still. Strictly there is not a
matter of CRPS yet.
Remarkably is the fact, that CRPS in old literature is called “Autonomic reflex
dystrophy”. That term has been lost by new immunologically insights about the
origin of CRPS. However this old aetiology is returning with this model.
A situation in which the concentrations of PGF and PGE both are laying between
ten and hundred ng/ml can be called as threatening CRPS.

Threatening CRPS

There are two possibilities. One from a cold starting position and one from a

This example
is a cold one. The resultant effect is a vasoconstriction.
If the positions of F and E have been interchanged
the resultant effect is a vasodilation.
This position is very risky. A little
event can cause a vasoconstriction with positive feedback, a situation, as one
can see in case of the seldom occurring disease
of Rye, or a vasodilation with positive feedback like CRPS.
Autonomic stimulation with cold stress, producing PGE, gives rise to a CRPS.
In case of a cold starting position questionnaires will be negative. In case of
a warm starting position some questionnaires will be positive. By some
researchers this position will be called as CRPS too, but strictly it is not a
CRPS. The feedback possibilities are still negative.

When the PGE concentration passes 100 ng/ml there is definitely an active CRPS.

Active CRPS

F is
producing a vasodilation. E produces now inflammation and vasodilation. There
exists an active positive feedback. Every counteraction is intensifying the
inflammation process. As prof Huygen wrote in his dissertation already: It is
nearly impossible to set off the inflammation process. And it is. Nearly. In
physics such situations are well-known. There exist two types of interventions.
More about that in the post about therapeutic possibilities. They are!

The actual value of this model
This model is not a
pure academic one. In my opinion medical research must have an intention of
practical application. Prevention and curing of diseases, that are the essentials of medicine. And a
model ought to serve this principle too.
So there are practically aspects.
First, because it clarifies that chronic pain and CRPs are not separate
conditions, but phases of the same disease. Indeed disease and not a psychological
circumstance or some kind of syndrome.
It shows, that chronic pain and CRPS could be consequences of preceding
accidents with additional inflammations. The optical characteristics of
inflammation are disappearing, but in many cases prostaglandins and cytokines with
not physiologically concentrations are remaining with vasoconstriction and
nerve stimulation as a result. So a fundamentally locally biochemical process
can have an extensive continuation in the central nervous system, with a virtually
realisation of a copy of the original process in that nervous system, proceeded
up to the pain centres in the brains.
Herefore others found arguments in the last years.
The fundamentally local processes are appearing in the skin, functioning as
an interactive human monitor, interacting actively by reflexes with visceral,
skeletal, muscular and connective tissue, parts of the same segment. In
generally they are hidden for the naked eye, but not for infrared equipment.
So it had been possible to overlook these processes during more than hundred
years and still!
In the second place shows the model the different representations of chronic
pain as precursors of CRPS. Representations, which are simply measurable and
testable. As a result of that possibilities
are existing to avoid CRPS by small operations.
In the third place the model facilitates aimed and rational therapeutic actions.

I am aware of the weight of this claim, but I used the techniques during 40
years without knowing why. And it had worked and more: those techniques are
obvious testable. But as in each science: It takes more than one swallow to
make a summer. Let them come. Structured repetition is needed. And for that a
model is serving too.

Henk van der Veen.

24-augustus 2018

Diagnostics in Chronic pain and CRPS

diagnostic possibilities Posted on Tue, July 31, 2018 13:22:01

Diagnostics in Chronic pain and CRPS.
Infrared thermography.

Methods of diagnostically testing.
Infrared thermography has been described extensively already in previous posts just as physically examination
by doctors.
The leading principle in medical examination is physically at first. After that
technically examination may be followed.
One single examination with infrared thermography is enough to direct the
diagnosis, but it is often not enough for a properly diagnosis. It gives the possibility to find
out the temperature of the pain area: warmer or colder than the referential
area. The referential area is the zone around the pain area or the counter side
in right or left sided pain. That temperature is important as well. Only two examination technics exist for
determining the differences in skin temperature: technetium scanning and
infrared thermography.
Technetium is a radio-actively drug
with lightly radiation properties,
produced in a few centres of the world. In the Netherlands it is produced in
the reactor centre, located in Petten and only for medical use.
The drug is injected and accumulates in places with upgraded blood
perfusion. Consequently the radiation
accumulates too. With specially scanning equipment it is possible to measure
that radiation. Reversely the radiation has been diminished in case of
downgrading the blood perfusion.
In the eighties researchers had found a relationship between the radio-active radiation
of technetium from painful skin areas and infrared thermography measurements.
Infrared thermography is not damaging for environment and human beings and is
also the preferred method for technical pain research. Unfortunately Infrared
thermography is a rather unrecognized technique.

Warm pain

Pain in a warm environment needs in his classical way inflammation with the
symptoms: redness, and swelling . Chronic pain without a well-known cause shows
those symptoms only in case of CRPS.
25% of chronic pain is warm without
swelling and redness
, demonstrated by thermographically research . CRPS has
been investigated extensively, but warm chronic pain not. Still chronic warm
pain can be the representative of an inflammation, even with the lack of
swelling and redness.
Also there is no research about the question if warm chronic pain can be the
precursor of CRPS. And that is an important question.

Cold pain
70% of all chronic pain sites are cold
In relation to their referential. It is not clear which processes are
happening here in this tissue. It is never investigated. May be the results of
CRPS research can help.
CRPS is a furious inflammation, hardly to stop, but in the end phase of it
there is not any visible inflammation anymore. Thermographically the tissue is cold, like the “normal” chronic pain.

An acute CRPS with pain, swelling, redness.

Biochemical investigation of the skin tissue of cold CRPS is showing the same inflammatory cytokines like TNF-alpha as the active warm CRPS. So there must be an inflammation without redness and swelling. Cold inflammation.

CRPS is an inflammation with a (small) trauma in his history. Also chronic pain has a trauma history, sometimes years ago. And like CRPS there had been existed a resulting inflammation like bleeding, fracture or haematoma. Sometimes there is a visible scar, but in most cases, there is nothing more to see, except by thermographically measurements. The invisible scar is cold.

Fig.A Fig.B

The patient is lying in prone position from left
to right. You see the buttocks. Black is cold. The black area on the lower panel (fig
A) is a
non-visible scar, a residue from an old trauma (hematoma) before
treatment. Fig B is a picture after treatment. You see then a symmetrical image,
like a cassata. That’s the ideal healthy

So there is an analogue with CRPS. A cold area after a trauma with pain…..
Logically like CRPS you can expect the area contains inflammatory cytokines as TNF-alpha too.
Conclusion: a chronic low graded inflammation without warmth, redness and swelling is the most likely base of chronic pain without known aetiology. Thermographically the site is cold.
Modern research is necessary to find out this hypothesis. But the consequences are immense. The technique is simple, relatively cheap, already done and described in case of CRPS.
Who will be the first to do this in relation to Cold chronic pain?

As above described a single picture is giving only poor information.
Much more data are originated by a range of pictures in a test situation.
CRPS has been called “Autonomic Reflex dystrophy” In former times. That name is supposing the influence of the autonomic nervous system. One important test is using the activity of that system.

Normally (in healthy persons) the body temperature is lowering if the activity of the autonomous nervous system (sympathetic nervous system) has been stimulated. That is easy to realize. In some academic centres a “coolpack” is used. The temperature of a part of the body is cooled down under strictly regulated circumstances. But it possible on an easier way too. For a range of measurements at the upper extremities it is enough to cool down the feet’s and ankles in a little water basin with a temperature of 19 0C. Ten photographs within ten minutes. That’s all. Reversely for measurements at the legs one can do that with cooling down the hands and lower arms. The test is called: “Cold Stress Test”.

What can you see:

1. Cold areas become colder
2.Warm areas become colder
3. Cold areas become warmer
4.Warm areas become warmer.

In healthy persons temperature decrease is a normal reaction, but an increase is a pathologically reaction. What’s the consequence of this? At the same patient on the same moment it is possible to get both reactions: a decrease on the healthy side and an increase on the pain side. That is characteristic for (beginning) CRPS.
There are very clear similarities between chronic pain and CRPS, but they don’t form part of the regular medical science.
CRPS follows frequently small trauma’s. Chronic pain shows in his history frequent trauma’s , bleeding, hematoma’s or inflammation. In the final phase of CRPS scar tissue has been leaved.
Measuring with infrared equipment the area is COLD.
After recovery from a trauma, a bleeding, a hematoma or an inflammation sometimes a visible scar has been leaved, but looking with infrared light and special equipment one sees nearly always a scar: an area with decreased or increased temperature. Sometimes painful.

In only 5% of the cases painful areas are neutral in temperature. In 70% they are cold and in 25% warm. In the acute phase CRPS is always warm. Traumas, bleeding, fractures and inflammations are always warm in the acute phase too.

Fig C.

A patient
with a painful area shortly after a bladder catheterization. (Left). The
painful area is warm, but not swollen and no redness. The image reflect on the
skin an internal trauma as a result of catheterization. The right image after
three weeks: there is a lot of recovery. Neither visible scar nor visible

These thermographically data are known at the neurological clinic of the University of Sao Paulo in Brazil. There exists a professorship for Infrared Thermography.
But else?
In the Netherlands there is not any knowledge about the origin of chronic pain, although there is extensive knowledge about that in old German literature. (Before 1945), but nobody is reading scientifically literature in German language after 1945. However all this literature is still showing much evidence about the origin of chronic pain and possibilities to treat it.
Modern papers from 2008 (Groeneweg), 2014 (Arendt-Nielsen), 2012,2013,2014,2015 (van der Veen) are pointing at a somatically and not a psychologically cause of chronic pain, like CRPS.
In the case of CRPS the tissue contains inflammatory active proteins: cytokines, like TNF-alpha, both in the acute phase and in the final phase. Chronic pain areas are containing the same cytokines in the inflammatory phase. About the final phase we did not know anything in the absence of research data, but it looks realistic that the same cytokines are causing the pain in the “chronic pain phase”.
Like CRPS!
But there are essentially remaining questions.

1.Inflammation has an unbreakable relation with warmth, redness and swelling too.
Why thermography is showing a cold inflammation without swelling and redness?

2.Sympathetic stimulation is contracting the vessels. (Skin)temperature is decreasing as a result.
Why autonomic stimulation has the property to raise the local temperature in some chronic pain areas?

3.There are too many similarities between CRPS and chronic pain.
Is there any relationship between them? Can it be?

4.In old papers the so called “CRPS” has been described as “Autonomic reflex dystrophy”. That terminology has been leaved in favor of “CRPS”.
Is it yet possible, that autonomic (sympathetic) stimulation might provoke a process as “CRPS”?

The answer is: Yes, all this is possible and reasonable and verifiable with infrared thermography, followed by biochemically testing of tissue fluid from the measured places.

Why it has not been done this? I don’t know. Someone must be the first?
Maybe someone anywhere on the world in the future. You can hope so.

In post 16 the tests are described by means of a model of chronic pain, based on the origin of chronic pain as a chronic inflammation.

In post 17 specific therapeutic possibilities are described, based on this model.

Henk van der Veen
31 july 2018

Thesis part 3

future Posted on Sat, June 23, 2018 17:30:29

Post 14
Thesis Back to chronic pain and CRPS

Both diseases are originated from damaged body tissue. Every
kind of lesion gives rise to an inflammation process. Such a process is necessary
for tissue repair. During the inflammation different kinds of peptides(cytokines)and
prostaglandins are developed. These molecules are regulating the local
recovery. The concentrations are easily upgrading to 10 ng/ml. Redness,
swelling, pain and warmth are the results.
The PGF effect controls the process. Therefore the concentration of PGE has to
be higher than the concentration of PGF. Point “E” is closer to the switch
point “C” of the curve than point “F”. A
small upgrading of the concentration of PGE transfers point “E” to the red area beyond point “C”.

this area the possibility to control the inflammation diminishes very dramatically.
The properties of PGE are changed to
vasodilation and inflammation. That is the medical situation seen in CRPS.
With infrared thermography one sees an extended hot area in the swollen part of
the extremity.
The only opportunity to feed back for the organism is to upgrade the PGF
concentration. The resulting inflammation effect is the downgrading of the
temperature. Point “F” is moving to point “C”.
At the phase of recovering of the disease the concentrations of inflammatory
agents are decreasing. The concentration of PGE diminishes . The inflammation
is decreasing and the temperature of the sick area downgrades. One can see that
with the eyes and measure it with infrared thermography.
But still the concentration of PGE is greater than the concentration PGF.
(There is still vasodilation!).
With further downgrading of the concentration of PGE the regulation changes
The concentration of PGE is smaller than the concentration of PGF. It means
that the PGE gets the control of the regulation. Vasoconstriction appears.

But the concentration PGF is still high. The concentration
of the inflammatory active buddies too.
But the area, measured with infrared thermography is cold now.
There exists a cold inflammation, indeed.
That is the situation, researched at the Erasmus University in Rotterdam (2008).
In the tissue fluid of the “Cold CRPS patient” the same cytokines had been
found as in the acute stage.
That is in accordance with the model above.

In case of chronic pain there had been a lesion once. According to the
situation of CRPS inflammatory active cytokines are produced in the tissue in
the acute phase. Like CRPS in the recovery phase the painful area is , measured
with infrared thermography, cold. Like CRPS, the concentration PGE has to be lower
than the concentration PGF. Therefore the inflammatory active prostaglandin
buddies have to be still present in the tissue . And so there must be an cold
inflammation in areas with chronic pain.
As described, a little lesion or operation has the possibility now to upgrade
this situation to an active CRPS (again). So chronic pain and CRPS are not syndromes,
but diseases. They differ from each other only by the phase in the same process.

Next post Diagnostics

Henk van der Veen

Thesis part 2

future Posted on Wed, June 20, 2018 17:15:46

Post 13
The basics of automatic regulations
Curves and PGE-PGF places on it.

example: Point “F” has been located on
the descending leg of the curve with a prostaglandin PGF concentration between
1 and 10 nanogram/ml tissue fluid. (1 nanogram is one billionth of a gram.)(X-axis)
The magnitude of the effect is between half max and max. (Y-axis).
Point “E” has a concentration between 10
ng/ml and 100 ng/ml (X-axis). The magnitude of the effect is between half max
and zero (Y-axis).
In this example the effect of “F” corresponds to three times the effect of “E”.
The concentration however is smaller than one fiftieth of the concentration of “E”.
The effect of “F” is vasodilation. The effect of “E” is vasoconstriction. The
net result in this example is a “moderate vasodilation”. However, the
concentration of the vasoconstrictor is substantially more than that of the
vasodilator. Like this a low concentration of an inhibiting molecule is blocking
a (too) high concentration of an opposite working molecule. This is called a negative
The gynaecological example in post 12 shows physiological concentrations between
100 picogram/ml and 1000 picogram/ml (one picogram is one thousandth of a
nanogram). In this example the green area.
“Vasodilation” as a term of the activity of PGF can be changed in “lower sweating”,
“more activity of the function of the gut”, “a lower airway resistance”, “better
perfusion of the skin, connective tissue and muscles”. It is a situation in
which inflammations can be developed.
For instance: a beginning influenza (flu) starts with vasoconstriction and a
cold. One is feeling cold too.
The body temperature is lowering for a while. Suddenly that is changing in temperature
upgrading and inflammation symptoms. In line with the model it means, that in a
healthy situations both the concentration and effect of PGE and that of PFG has
been located in the green area. In case of symptoms of disease point “B” of the
curve is passed. Cold feelings and temperature downgrading can be started as a
result of upgrading of the concentration of PGF. The PGF effect is downgrading
then and the result from PGE and PGF is a PGE effect: vasoconstriction.

This example shows the situation in which the PGF-PGE
balance is resulting in a PGE effect.
It shows a “moderate vasoconstriction”.
In this situation the term of activity of PGE :“Vasoconstriction” can be
changed in :”sweating”, ”spastic guts”, “difficult defecation”, “spastic
airways”, “viscous mucus”,” downgraded perfusion of the skin, connective tissue
and muscles”, “Muscle spasms” and “lowering of the body temperature”.
All these are symptoms, emerging in the pre-phase of a flu.

For the advanced

all the described symptoms have been the result of a relationship between
prostaglandins and Calcium ions, outside and inside a cell. If these ions from
outside are passing the especially Calcium gates and not have been bound to especially
peptides(Calmodulin) into the cell they are attached to small muscle fibers. The
result is contraction. Just that is the property, which viruses need for cell
injection and reduplication. Then the puzzle remains: Why and how the symptoms are starting with fever, vasodilation and so on? There is
an answer:
The dose-effect curve has the same fluent form for both antagonists. An abrupt
moment only arises if one of them passes point “C” of the curve. If PGE passes
point “C” the intrinsic property of vasoconstriction changes into vasodilation.
The vasodilation property of PGF is upgraded by PGE.
That is called a “positive feed-back”.
The resulting effect is an inflammation.
In all the modern literature PGE is called an inflammation active substance. But
the reality is, that in modern experiments the test- dose always is higher than
100 ng/ml tissue fluid. And indeed: in that concentrations PGE has an inflammation
effect, but not in physiologically circumstances.

Positive feed-back mechanisms are dangerous. The cross-current is missing and
the process might to be unstoppable. That is the situation around CRPS.
In the audio technique this phenomenon has been known as: acoustic feed-back.
If a microphone is standing too nearby a speaker a shrill beep can ravage the
ears! Also this phenomenon is a result of positive feed-back. The descending
line of the curve is the most hazardous. Also in audio technique.
In human bodies one can expect diseases, if the prostaglandin concentrations
come along these line of the curve.

Next post (14): back to Chronic pain and CRPS

Henk van der Veen

Thesis part 1

future Posted on Tue, June 19, 2018 17:12:25

Post 12
The thesis itself.

The human body functions as a fully automated system. It has been told in previous posts.
Body temperature and biochemical processes are adjusted accurately without active humanly actions.
Therefore it is amazingly that the knowledge about that is missing to a high degree.
We know, that the autonomous nervous system plays an important role and we know that functioning of organs are modulated by hormones.

The upper curves are the concentration curves of estrogen and progestogen during the monthly female cycle. Smoothly and without any switching moments in the first two weeks. On the other hand the BBT (Basal Body Temperature) shows sharply peaks and dips.
The third curve is a calculated curve based on the switching properties of the prostaglandins , applied to the concentrations of the hormones. The lowest curve is an original BBT curve.
The original BBT curve and the reckoned one are very similar.
It has been known that prostaglandins modulate and regulate the action of hormones. The method of issue has not been documented yet. But the switching possibilities of them are looking very impressive.
All natures activities around the ovulation, reflected into the body temperature has been seen in the reckoned curve too.

Switching functions
A switching function is an abrupt effect and not a fluently process. Everyone, who used a switch once in lifetime is knowing that.
An example: opening or closing a bridge is possible with the same switch. Two contrarily actions with the same button, activated in a split second.
Not known in the modern medicine, a similar biologically switch has been described in 1977 already.
Unfortunately that know-how had been too specialized for reaching the medical world. It is still waiting. The remarkable molecules having the property to produce two opposite effects have been described in the posts about prostaglandins.
But only one molecule with switching properties is not enough. In stable measure- and regulation systems there always exist two opposite action systems to balance each other.

Biological switches
In the biologically world two types of opposite functioning prostaglandins are existing too, balancing each other. They had been researched and described as “vasodilatative” and “vasoconstrictive”, bound to a vasoconstrictive molecule. But as buddies to another pharmacologically active molecule they are doing much more. Bound to a hormonal system as the gynecologically combination estrogen-progestogen they have the ability to manage the body temperature. Result: the BBT.

Theoretically the prostaglandins can be the link between the activity of the nervous system and the local biochemically processes. They can be the link between hormone concentrations and the effects attributed to hormones. Thereby they have the ability to switch. The curves, described by Horrobin and Manku are showing unmistakably that switch momentum: vasoconstriction to vasodilatation. Theoretically one molecule may be sufficient for changing the effect.
As told earlier: two prostaglandins are known with switching properties: PGE and PGF. Only by one Hydrogen ion they are differing from each other. The biological system is able to change enzymatically PGE into PGF in a reversible way. At low physiologically concentration PGE is acting vasoconstrictive and PGF vasodilatative. At high concentration the effects are reversed.
The effect of PGE minus the effect of PGF or vice-versa is presenting the resulting effect of both of them. Both prostaglandins have the same dose-effect curve. It means, that graphically the effects of both molecules are represented in a place on that curve.

Next post: Curves and PGE-PGF places on them.

Henk van der Veen

19 June 2018

background part 2

future Posted on Sat, June 02, 2018 10:52:19

Post 11

Biochemically there is one substance, which has a role in pain, infection, inflammation, nerve activation, local anaesthesia, vasodilation and vasoconstriction together: the prostaglandins.
For inflammation they need to be bound on cytokines: inflammatory active proteins.
For vasoactive processes, they need to be bound on natural vasoactive proteins, like adrenalin and noradrenalin. Only in cooperation with proteins with a specific biologically action they can work.
In general prostaglandins do have two actions: they are sizing the magnitude of the effect of the effector and the art of the effect. They can design the art of the biochemically function of the active proteins. An example: they can change the activity of noradrenalin from vasoconstriction to vasodilation, just the opposite.

Normally in medical science one presumes, that a dose-effect curve for biologically action is a linear one. More prostaglandins the more effect. But research about prostaglandins already in 1977 showed another dose-effect curve: the “bell shaped” one.

Between point “A” and “B” one can see a top of the curve. This curve is not a linear one. The concentration has been plotted logarithmically at the X-axis.
The top has been reached with a concentration of 1 nanogram/millilitre. Point “C” has been reached with a concentration of 100 nanogram/millilitre.
That’s very interesting. More than 1 ng/ml downgrades the prostaglandin effect.
More than 100 ng/ml changes the effect to the opposite.
So a vasoconstrictive prostaglandin in low doses (like PGE) is acting like a vasodilatative one (like PGF) in high doses. In inflammation with high concentrations PGE the skin tissue is reacting with vasodilation and exudation. The temperature of the skin tissue is then high. Returning to the healthy situation the concentration PGE is downgrading. As an example: the concentration PGE has been decreased so that the effect in excitation is on point “B”’ . Prostaglandin-“E” is acting vasoconstrictive. The temperature of the skin is much lower now than in the acute phase, but higher than with a concentration of 1 ng/ml. Yet the concentration in “B” is scarcely lower than 100ng/ml.
Above the concentration of 100 ng/ml PGE does enhancing the opposite PGF.
PGE has been reported as a pain generator too.
PGF has an opposite effect in relation to PGE. Above 100 ng/ml it is acting like PGE in low dose.
In a living organism the result of the both types together defines the final result.
As you can see the final result is dependent on the place of each prostaglandin effect upon the curve. That place is dependent on the concentration of the prostaglandin.
The final result, applied to vasoactive situations, gives vasodilation with upgrading skin temperature or vasoconstriction with downgrading temperature. That can be measured with infrared thermography. But a good explanation of the results is not easy.

An example:
After a fracture or an operation there is a release of a lot of cytokines, bound to prostaglandins (PGE and PGF). IF both the concentrations of PGE and PGF are smaller than 100 ng/ml and higher than 1 ng/ml the smallest concentration is essential for the resulting effect. Because of the smallest concentration is delivering the highest place on the curve.

In this example point “F” has a concentration smaller than 10 ng/ml and point “E” has a concentration higher than 10 ng/ml. The resulting effect is F-E and F>E.
In this example too there is a vasodilation, which can be measured by infrared thermography.
In most physiologically healthy situations the concentrations prostaglandins are varying between picograms/ml and 1 nanogram/ml. In vigorously situations till 10 nanogram/ml. So there is a safety area of changing in concentrations. Estimated about a hundred times.

This curve shows a moderate inflammation, one can expect in case of a moderate appendicitis.
Theoretically one can measure this with infrared thermography and on a biochemically way in skin tissue fluids. Not the prostaglandins itself, but still the cytokines onto the prostaglandins have been bound.
Reversely, changing F and E, exists a vasoconstriction: a situation after recuperation in case of an infection.
You see here a working modulating and regulating system of a living organism with a biochemically switch at point “C”.
There is no other modulating and regulating system known or described in living organisms.

And yes: Hormonal regulating is carried out by prostaglandins too. Applied to hormonal changes in the womanly cycle the model is published in 2015. Just as other biochemically active molecules hormones are bound with prostaglandins as a buddy. Without these buddies hormones does not have any activity.
This model can explain the strange ambiguous findings mentioned above in this post. How ? That is, what you can read in the theoretical model itself.
These posts are written only for step by step approaching the basics of this model.

In the next posts: the model itself and (more important) what can you do with that?

Henk van der veen
2 June 2018

Background thesis part 1

future Posted on Mon, May 28, 2018 22:42:57

Post 10

Background thesis.

From the preface has been demonstrated, that chronic pain detectable is in the SKIN. It has been originated as a result of bleeding, inflammation, bone fracture, operation or another kind of trauma in the skin directly. But not only directly. Also as a result of a combination of these factors in bones, joints, connective tissue, muscles and viscera. In this cases there has been an activation of visceral-cutaneous reflexes, ended in the skin. The visceral pain is nauseous and without the possibility of localisation. In combination with the skin component the pain is discernable in the same segment as the originating disease. The activity of this disease had been expanded to all the segment parts.

That is giving possible problems with differential diagnostics.

An example:

An appendicitis normally is giving pain in the point of Mc Burney right down in the belly.

But the appendix has been located in the eleventh thoracic segment. As a result of this the eleventh intercostal muscle may start contracting too. In that case the pain starts in the upper part. In many cases this is leading to the misdiagnosis of a disease in the bladder.
Low back pain on the right side is another misleading symptom in the beginning of an appendicitis: Groups of fibres of the “Musculus Obliquus Abdominus” have been innervated from the same segment.
For a practioner the differential diagnosis is easy, based on physical signs.

After removal of an appendix a form of pain can left over. Mostly after a symptom less duration of three till six months. That kind of pain has been settled in the skin and in most cases it is chronic. After local anaesthesia in the skin the pain has been disappeared. The duration of this phenomenon can be twenty minutes to some days…. That is strange. The pharmacological time of working of the anaesthesia is about twenty minutes. What is happening in the organism after these twenty minutes ?. It is certainly NOT a jammed nerve. In that case the pain free duration is at maximum the duration of the effect of the anaesthesia. If the pain disappears for more than 24 hours there is another strange phenomenon: repetition of the anaesthetics leaves the pain for 48 hours, after another repetition about 96 hours and so on. Logarithms. Why ? These technique has been known as “Neuraltherapy” and has been used since 1925 mostly in Germany.

A third strange diagnostic finding is a result of infrared thermography (skin temperature measurement). The pain area described above is in thermographically measurement cold: the temperature is lower than the surrounding area. In the acute phase the area is warm. But when the infection has been gone. Why did the temperature not return to the normal state?

This example is presuming that “warm” is a property of an acute process and “cold” the property of an old process. Like a scar or a strangulated nerve. But in case of CRPS the end phase is Cold and yet there are inflammatory active cytokines. The same cytokines as in the warm acute phase and yet the skin is cold. It suggests there is still an inflammation. But inflammations have been considered to be warm, red and swollen. Why cold? And if there is an inflammation, is it possible that an inflammation exists in chronic pain areas too?

Is it possible to find a way to explain this?
Yes there is such a way:

next post: part 2

Henk van der Veen

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