En weer valt een biopsychosociaal sprookje in duigen...
Volgens het proefschrift en onderliggende studies van onderzoekster Karin Jensen:
- is het pijndempende mechanisme in de hersenen duidelijk verstoord, en
is dit niet het gevolg van depressiviteit, "pijnkatastrofering" etc. (Nijs:
klik hier en
- lijkt er sprake van een genetische aanleg voor fibromyalgie (COMT polymorfisme,
COMT: een enzym dat catacholaminen/stresshormonen, bijv. dopamine en adrenaline, afbreekt).
- neemt de pijngevoeligheid selektief af m.b.v. milnacipran: een antidepressiva,
niet omdat patiŽnten depressief zijn, maar als gevolg van andere effekten van dit middel.
- is het zaak fibromyalgie serieus te nemen/zo snel mogelijk diagnostiseren,
omdat naarmate iemand langer ziek is/meer pijn ervaart, de werking van dit middel afneemt.
Voor berichtgeving in de media klik op een van onderstaande logo's:
Early treatment of fibromyalgia more effective
[PRESS RELEASE 22 October 2009]
People suffering from fibromyalgia have reduced activity in the parts of the brain that inhibit the experience of pain.
Drugs that affect the CNS can be effective against the disease, and are thought to be even more so if administered early in its course.
This according to a new thesis from Karolinska Institutet.
"It's a common misconception that fibromyalgia is a manifestation of mental problems,"
says Karin B. Jensen, postgraduate at the Department of Clinical Neuroscience. "
But in the studies that comprise my thesis,
we've made careful measurements and have found
no correlation at all between pain sensitivity in fibromyalgia patients and the degree of anxiety or depression they show."
In one of the studies presented in the thesis,
subjects had both thumbs pressed hard enough for them to feel the same degree of mild pain as healthy controls.
Using functional magnetic resonance imaging (fMRI), researchers could show that
the subjects had the same level of activity in the parts of the brain
that deal with emotions as well assensory information from the thumb,
regardless of which group they belonged to.
However, the subjects with fibromyalgia had lower activity in a brain area that inhibits the experience of pain.
According to the team,
treatment with drugs that work on the central nervous system (CNS), such as SNRI antidepressants,
are effective against fibromyalgia.
But this is not a question of treating depression but of other properties of these drugs.
"The patients who had had their pain symptoms for the shortest amount of time
were those that responded best to the drug treatments tested," says Karin B Jensen.
"This shows how important it is that fibromyalgia is detected and taken seriously as early in its development as possible."
Her thesis also confirms the existence of a relationship between genetics and pain regulation.
Studies of healthy people revealed a relationship between a specific genetic variant and the effect of a morphine-like drug on repeated pain stimulation.
The results suggest that the gene under study only affects the body's pain regulating system in the presence of greater psychological stress.
This knowledge, say the researchers, could one day make possible the development of customised medical treatments and thus better and more effective pain relief.
Fibromyalgia affects about two per cent of the population, women more so than men.
The disease involves the enhancement of pain impulses, leaving sufferers highly sensitive to pain, which is both chronic and diffuse.
Previously, the causes of the disease were unknown, and there were no objective measurements of the way the CNS processes pain.
This, in turn, made many sufferers feel misunderstood and mistreated by the healthcare services and during rehabilitation.
Brain mechanisms in pain regulation, Karin Jensen, Department of Clinical
Neuroscience, Karolinska Institutet. Supervisors: Professor Martin
Ingvar and associate professor Eva Kosek.
The thesis defence is scheduled for Friday 23 October 2009.
Brain mechanisms in pain regulation
Jensen, Karin B
Fredagen den 23 oktober 2009, kl. 13.00.
Karolinska Institutet, Hillarpsalen, Retzius všg 8.
ISBN: 978-91-7409-646-0, Diss: 09:304.
The subjective sensitivity to pain
between individuals and
has contributed to
the understanding of
the cerebral mechanisms
involved in pain regulation.
The descending pain inhibitory circuitry
is a well defined cerebral network
afferent nociceptive information.
The aim of this thesis
was to investigate
different aspects of
in patients with Fibromyalgia (FM)
as well as
the impact of
specific genetic variations
on pain sensitivity dynamics
in healthy subjects.
patients with FM
an impaired mechanism
for descending pain inhibition and
was paired with
a diminished activation of
the rostral anterior cingulate cortex and
two regions that
play an important role
in descending pain regulation.
These results advance
the understanding of
in FM and
new directions for
the development of
the possible impact of
negative mood on
in patients with FM and
during experimental pain
was not modulated
by depressive symptoms,
The activity of
the brain regions
previously implicated in
the pathophysiology of FM
were not correlated with
high ratings of negative mood
which suggests that
two segregated cerebral mechanisms
In study III
patients with FM
were treated with
a Noradrenaline-Serotonin Reuptake Inhibitor (milnacipran) or
for 12 weeks.
an improvement of symptoms
both milnacipran and
were compared and
results revealed that
sensitivity to pressure
in milnacipran responders.
This decreased sensitivity
also correlated to
the improvement of
ongoing clinical pain.
The study suggests that
the specific effect of
direct antinociceptive effects and/or
by the strengthening of the
endogenous pain inhibitory mechanisms.
In study IV
the genetic influence
on the descending pain inhibitory function
in healthy subjects
Results demonstrate that
a genetic polymorphism (COMTval158met)
with influence on
the function of
the noradrenergic and
is related to
the response dynamics of
repeated pain stimulations
following opioid administration.
Results suggest that
the initial pain response
is not influenced by the COMTval158met polymorphism
but when the system is challenged
the difference is expressed.
Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain.
Pain. 2009 Jul;144(1-2):95-100. Epub 2009 May 1.
Jensen KB, Kosek E, Petzke F, Carville S, Fransson P, Marcus H, Williams SC, Choy E, Giesecke T, Mainguy Y, Gracely R, Ingvar M.
Over the years, many have viewed Fibromyalgia syndrome (FMS) as a so-called "functional disorder" and
patients have experienced a concomitant lack of interest and legitimacy from the medical profession.
The symptoms have not been explained by peripheral mechanisms
alone nor by specific central nervous system mechanisms.
In this study, we objectively evaluated the cerebral response to
individually calibrated pain provocations of a pain-free body region (thumbnail).
The study comprised 16 female FMS patients and 16 individually age-matched controls.
Brain activity was measured using functional magnetic resonance imaging (fMRI)
during individually calibrated painful pressures representing 50 mm on a visual analogue scale (VAS) ranging from 0 to 100 mm.
Patients exhibited higher sensitivity to pain provocation than controls
as they required less pressure to evoke equal pain magnitudes (U(A)=48, p<.002).
Despite lower pressures applied in patients at VAS 50 mm,
the fMRI-analysis revealed no difference in activity in brain regions
relating to attention and affect or regions with sensory projections from the stimulated body area.
However, in the primary link in the descending pain regulating system (the rostral anterior cingulate cortex)
the patients failed to respond to pain provocation.
The attenuated response to pain in this brain region
is the first demonstration of a specific brain region
where the impairment of pain inhibition in FMS patients is expressed.
These results validate previous reports of dysfunctional endogenous pain inhibition in FMS and
advance the understanding of the central pathophy≠siolo≠gic mechanisms,
providing a new direction for the development of successful treatments in FMS.
PMID: 19410366 [PubMed - indexed for MEDLINE]
Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT val(158)met polymorphism.
PLoS One. 2009 Jun 23;4(6):e6016.
Jensen KB, Lonsdorf TB, Schalling M, Kosek E, Ingvar M.
Increased pain sensitivity
after opioid administration (opioid-induced hyper≠algesia) and/or
repeated painful stimuli
is an individually varying and clini≠cally important phenomenon.
The functional polymorphism (val(158)met) of the Catechol-O-methyltransferase (COMT) gene regulates the metabolism of dopamine/noradrenaline.
Individuals homozygous for the met(158) allele have been reported to have increased pain sensitivity and
there are findings of lower micro-opioid system activation during sustained pain.
We hypothesized that met/met individuals would exhibit
higher pain sensitization and opioid-induced hyperalgesia
in response to repeated pain stimuli and an intravenous injection of an opioid drug.
Participants were 43 healthy subjects
who went through an experiment where five blocks of pain were induced to the hand using a heat probe.
After each stimulus subjects rated the pain on a visual analogue scale (VAS) from 0 mm (no pain) to 100 mm (worst possible pain).
Before the second stimulus there was an intravenous injection of a rapid and potent opioid drug.
At baseline there was no difference in pain ratings between the COMTval(158)met genotypes, F(2, 39)<1.
However, a repeated measures ANOVA for all five stimuli revealed a main effect for COMTval(158)met genotype, F(2, 36) = 4.17, p = 0.024.
Met/met individuals reported significantly more pain compared to val/val, p = 0.010.
A pairwise comparison of baseline and the opioid intervention demonstrated that
analgesia was induced in all groups (p = 0.042) without a separating effect for genotype (n.s).
We suggest that the initial response of the descending pain system is not influenced by the COMTval(158)met polymorphism
but when the system is challenged the difference is revealed.
An important clinical implication of this may be that
the COMTval(158)met related differences
may be more expressed in individuals
where the inhibitory system is already challenged and sensitive, e.g. chronic pain patients.
This has to be proven in future studies where the impact of the COMTval(158)met polymorphism on opioid treatment in patients is addressed.
PMID: 19547755 [PubMed - in process]
Uitgebreid verslag van deze studie:
Met dank aan Dirk.