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 hier).

• 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 patiënten 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:

Persbericht

Early treatment of fibromyalgia more effective

[PRESS RELEASE 22 October 2009]

http://ki.se/ki/jsp/polopoly.jsp?d=130&a=85945&l=en&newsdep=130

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.

Thesis:

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.

Proefschrift

Brain mechanisms in pain regulation

Jensen, Karin B

Fredagen den 23 oktober 2009, kl. 13.00.

Karolinska Institutet, Hillarpsalen, Retzius väg 8.

ISBN: 978-91-7409-646-0, Diss: 09:304.

http://diss.kib.ki.se/2009/978-91-7409-646-0/thesis.pdf

Abstract:

The subjective sensitivity to pain

differs greatly

between individuals and

neuroimaging

has contributed to

the understanding of

the cerebral mechanisms

involved in pain regulation.

The descending pain inhibitory circuitry

is a well defined cerebral network

that enables

regulation of

afferent nociceptive information.

The aim of this thesis

was to investigate

different aspects of

pain modulation

in patients with Fibromyalgia (FM)

as well as

the impact of

specific genetic variations

on pain sensitivity dynamics

in healthy subjects.

Study I

demonstrated that

patients with FM

had

an impaired mechanism

for descending pain inhibition and

that

this deficiency

was paired with

a diminished activation of

the rostral anterior cingulate cortex and

the brainstem,

two regions that

play an important role

in descending pain regulation.

These results advance

the understanding of

the pathophysiology

in FM and

provide

new directions for

the development of

effective treatments.

Study II

investigated

the possible impact of

negative mood on

pain processing

in patients with FM and

found that

brain activity

during experimental pain

was not modulated

by depressive symptoms,

anxiety, or

catastrophizing thoughts.

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

there are

two segregated cerebral mechanisms

dealing with

pain and

negative mood

in FM.

In study III

patients with FM

were treated with

a Noradrenaline-Serotonin Reuptake Inhibitor (milnacipran) or

placebo

for 12 weeks.

All patients

that reported

an improvement of symptoms

after treatment,

including

both milnacipran and

placebo responders,

were compared and

results revealed that

sensitivity to pressure

improved selectively

in milnacipran responders.

This decreased sensitivity

also correlated to

the improvement of

ongoing clinical pain.

The study suggests that

the specific effect of

milnacipran

acts through

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

was assessed.

Results demonstrate that

a genetic polymorphism (COMTval158met)

with influence on

the function of

the noradrenergic and

dopaminergic systems,

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.

Studie 1

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 pathophy­siolo­gic mechanisms, providing a new direction for the development of successful treatments in FMS.

PMID: 19410366 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/19410366

Studie 2

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 hyper­algesia) and/or repeated painful stimuli is an individually varying and clini­cally 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]

PMCID: PMC2695541

Uitgebreid verslag van deze studie:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695541/pdf/pone.0006016.pdf

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006016

Met dank aan Dirk.