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The translocator pr...
The translocator protein gene is associated with symptom severity and cerebral pain processing in fibromyalgia
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- Kosek, Eva (författare)
- Karolinska Institutet
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- Martinsen, S. (författare)
- Karolinska Institutet
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- Gerdle, Björn (författare)
- Linköpings universitet,Avdelningen för samhällsmedicin,Medicinska fakulteten,Region Östergötland, Smärt och rehabiliteringscentrum
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- Mannerkorpi, Kaisa, 1955 (författare)
- Gothenburg University,Göteborgs universitet,Centrum för personcentrerad vård vid Göteborgs universitet (GPCC),Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,University of Gothenburg Centre for person-centred care (GPCC),Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg, Sweden
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- Lofgren, M. (författare)
- Karolinska Institutet
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- Bileviciute-Ljungar, I. (författare)
- Karolinska Institutet
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- Fransson, P. (författare)
- Karolinska Institutet
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- Schalling, M. (författare)
- Karolinska Institute, Sweden
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- Ingvar, M. (författare)
- Karolinska Institutet
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- Ernberg, M. (författare)
- Karolinska Institutet
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- Jensen, K. B. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier BV, 2016
- 2016
- Engelska.
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 58, s. 218-227
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The translocator protein (TSPO) is upregulated during glia activation in chronic pain patients. TSPO constitutes the rate-limiting step in neurosteroid synthesis, thus modulating synaptic transmission. Related serotonergic mechanisms influence if pro- or anti-nociceptive neurosteroids are produced. This study investigated the effects of a functional genetic polymorphism regulating the binding affinity to the TSPO, thus affecting symptom severity and cerebral pain processing in fibromyalgia patients. Gene-to-gene interactions with a functional polymorphism of the serotonin transporter gene were assessed. Fibromyalgia patients (n = 126) were genotyped regarding the polymorphisms of the TSPO (rs6971) and the serotonin transporter (5-HTTLPR/rs25531). Functional magnetic resonance imaging (n = 24) was used to study brain activation during individually calibrated pressure pain. Compared to mixed/low TSPO affinity binders, the high TSPO affinity binders rated more severe pain (p = 0.016) and fibromyalgia symptoms (p = 0.02). A significant interaction was found between the TSPO and the serotonin transporter polymorphisms regarding pain severity (p < 0.0001). Functional connectivity analyses revealed that the TSPO high affinity binding group had more pronounced pain-evoked functional connectivity in the right frontoparietal network, between the dorsolateral prefrontal area and the parietal cortex. In conclusion, fibromyalgia patients with the TSPO high affinity binding genotype reported a higher pain intensity and more severe fibromyalgia symptoms compared to mixed/low affinity binders, and this was modulated by interaction with the serotonin transporter gene. To our knowledge this is the first evidence of functional genetic polymorphisms affecting pain severity in FM and our findings are in line with proposed glia-related mechanisms. Furthermore, the functional magnetic resonance findings indicated an effect of translocator protein on the affective-motivational components of pain perception.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Fibromyalgia
- Translocator protein
- Serotonin
- Genetic polymorfisms
- Functional magnetic resonance
- serotonin transporter gene
- central-nervous-system
- 18 kda tspo
- mitochondrial dysfunction
- neuropathic pain
- functional connectivity
- benzodiazepine-receptor
- central inflammation
- therapeutic target
- substance-p
- Immunology
- Neurosciences & Neurology
- Fibromyalgia; Translocator protein; Serotonin; Genetic polymorfisms; Functional magnetic resonance imaging; Serotonin transporter; SCL6A4; rs6971; 5-HTTLPR; Gene-to-gene interactions
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Kosek, Eva
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Martinsen, S.
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Gerdle, Björn
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Mannerkorpi, Kai ...
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Lofgren, M.
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Bileviciute-Ljun ...
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Fransson, P.
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Schalling, M.
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Ingvar, M.
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Ernberg, M.
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Jensen, K. B.
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
- Artiklar i publikationen
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Brain Behavior a ...
- Av lärosätet
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Göteborgs universitet
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Linköpings universitet
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Uppsala universitet
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Karolinska Institutet