The translocator protein gene is associated with endogenous pain modulation and the balance between glutamate and gamma-aminobutyric acid in fibromyalgia and healthy subjects [Elektronisk resurs] a multimodal neuroimaging study

• 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

Medical and Health Sciences  (hsv)

Clinical Medicine  (hsv)

Neurology  (hsv)

Medicin och hälsovetenskap  (hsv)

Klinisk medicin  (hsv)

Neurologi  (hsv)

Genre

government publication  (marcgt)

Indexterm och SAB-rubrik

Fibromyalgia

TSPO

Genetic polymorphism

Endogenous pain modulation

MRS

Glutamate

GABA

rACC

Thalamus

fMRI