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, SilviaKarolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden. (author)

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

Article/chapterEnglish2022

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2021-04-09
Ovid Technologies (Wolters Kluwer Health),2022
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-467985
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-467985URI
https://doi.org/10.1097/j.pain.0000000000002309DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
Fibromyalgia
TSPO
Genetic polymorphism
Endogenous pain modulation
MRS
Glutamate
GABA
rACC
Thalamus
fMRI

Added entries (persons, corporate bodies, meetings, titles ...)

Sandstrom, AngelicaKarolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden. (author)
Tour, JeanetteKarolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden. (author)
Kadetoff, DianaKarolinska 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. (author)
Schalling, MartinKarolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden. (author)
Jensen, Karin B.Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden. (author)
Sitnikov, RouslanKarolinska Univ Hosp, MRI Res Ctr, Stockholm, Sweden. (author)
Ellerbrock, IsabelKarolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden. (author)
Kosek, EvaUppsala universitet,Klinisk smärtforskning,Karolinska Inst, Dept Clin Neurosci, Nobels Vag 9, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden(Swepub:uu)evako353 (author)
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)

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In:Pain: Ovid Technologies (Wolters Kluwer Health)163:2, s. 274-2860304-39591872-6623

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By the author/editor: Fanton, Silvia; Sandstrom, Angel ...; Tour, Jeanette; Kadetoff, Diana; Schalling, Marti ...; Jensen, Karin B.; show more...; Sitnikov, Rousla ...; Ellerbrock, Isab ...; Kosek, Eva; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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