The translocator protein gene is associated with endogenous pain modulation and the balance between glutamate and γ-aminobutyric acid in fibromyalgia and healthy subjects: a multimodal neuroimaging study.
Abstract: 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...
| Publicado en: | PAIN Vol. 163; no. 2; pp. 274 - 287 |
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| Autores principales: | , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Lippincott Williams & Wilkins
2/1/2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=154665373&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 154665373 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03043959 22N jtl: PAIN issn: 03043959 maglogo: N pubinfo: dt: 2/1/2022 vid: 163 iid: 2 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 154665373 154665373 NLM34142769 154665373 10.1097/j.pain.0000000000002309 NLM34142769 154665373 ppf: 274 ppct: 13 formats: tig: atl: The translocator protein gene is associated with endogenous pain modulation and the balance between glutamate and γ-aminobutyric acid in fibromyalgia and healthy subjects: a multimodal neuroimaging study. aug: au: Fanton, Silvia Sandström, Angelica Tour, Jeanette Kadetoff, Diana Schalling, Martin Jensen, Karin B. Sitnikov, Rouslan Ellerbrock, Isabel Kosek, Eva affil: Department of Clinical Neuroscience, Karolinska Insitutet, Stockholm, Sweden sug: subj: Fibromyalgia Receptors, Cell Surface GABA Metabolism Brain Pain Metabolism Pain Human Glutamic Acid Metabolism Glutamic Acid Receptors, Cell Surface Metabolism Neuroradiography Research Subjects Tomography, Emission-Computed Methods Comparative Studies Multicenter Studies Evaluation Research Validation Studies Clinical Assessment Tools ab: Abstract: 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 γ-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 γ-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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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