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The translocator pr...
The translocator protein gene is associated with endogenous pain modulation and the balance between glutamate and gamma-aminobutyric acid in fibromyalgia and healthy subjects : a multimodal neuroimaging study
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- Fanton, Silvia (författare)
- Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
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- Sandstrom, Angelica (författare)
- Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
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- Tour, Jeanette (författare)
- Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
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- Kadetoff, Diana (författare)
- Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.;Löwenströmska Hosp, Stockholm Spine Ctr, Upplands Väsby, Sweden.
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- Schalling, Martin (författare)
- Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden.
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- Jensen, Karin B. (författare)
- Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
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- Sitnikov, Rouslan (författare)
- Karolinska Univ Hosp, MRI Res Ctr, Stockholm, Sweden.
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- Ellerbrock, Isabel (författare)
- Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.
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- Kosek, Eva (författare)
- Uppsala universitet,Klinisk smärtforskning,Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden
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Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden. Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden.;Löwenströmska Hosp, Stockholm Spine Ctr, Upplands Väsby, Sweden. (creator_code:org_t)
- 2021-04-09
- 2022
- Engelska.
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 163:2, s. 274-286
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Abstract
Ämnesord
Stäng
- A cerebral upregulation of the translocator protein (TSPO), a biomarker of glial activation, has been reported in fibromyalgia subjects (FMS). The TSPO binding affinity is genetically regulated by the Ala147Thr polymorphism in the TSPO gene (rs6971) and allows for a subject classification into high affinity binders (HABs) and mixed/low affinity binders (MLABs). The aim of the present multimodal neuroimaging study was to examine the associations of the TSPO polymorphism with: (1) conditioned pain modulation, (2) expectancy-modulated pain processing assessed during functional magnetic resonance imaging, and (3) the concentration and balance of glutamate and gamma-aminobutyric acid in the rostral anterior cingulate cortex and thalamus using proton magnetic resonance spectroscopy in FMS (n = 83) and healthy controls (n = 43). The influence of TSPO on endogenous pain modulation presented in the form of TSPO HABs, as opposed to MLABs, displaying less efficient descending pain inhibition and expectancy-induced reduction of pain. Translocator protein HABs in both groups (FM and healthy controls) were found to have higher thalamic glutamate concentrations and exhibit a pattern of positive correlations between glutamate and gamma-aminobutyric acid in the rostral anterior cingulate cortex, not seen in MLABs. Altogether, our findings point to TSPO-related mechanisms being HAB-dependent, brain region-specific, and non-FM-specific, although in FMS the disadvantage of an aberrant pain regulation combined with an HAB genetic set-up might hamper pain modulation more strongly. Our results provide evidence for an important role of TSPO in pain regulation and brain metabolism, thereby supporting the ongoing drug development targeting TSPO-associated mechanisms for pain relief.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Fibromyalgia
- TSPO
- Genetic polymorphism
- Endogenous pain modulation
- MRS
- Glutamate
- GABA
- rACC
- Thalamus
- fMRI
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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