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

Pain. 2022 Feb 1;163(2):274-286. doi: 10.1097/j.pain.0000000000002309.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain
  • Fibromyalgia*
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism
  • Healthy Volunteers
  • Humans
  • Neuroimaging
  • Pain / diagnostic imaging
  • Pain / genetics
  • Pain / metabolism
  • Positron-Emission Tomography / methods
  • Receptors, GABA* / genetics
  • Receptors, GABA* / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Receptors, GABA
  • TSPO protein, human
  • Glutamic Acid
  • gamma-Aminobutyric Acid