Decreased neural inhibitory state in fibromyalgia pain: A cross-sectional study

Elif Uygur-Kucukseymen, Luis Castelo-Branco, Kevin Pacheco-Barrios, Maria Alejandra Luna-Cuadros, Alejandra Cardenas-Rojas, Stefano Giannoni-Luza, Huiyan Zeng, Anna Carolyna Gianlorenco, Marina Gnoatto-Medeiros, Emad Salman Shaikh, Wolnei Caumo, Felipe Fregni

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Objectives: Chronic pain is one of the most common and challenging symptoms in fibromyalgia (FM). Currently, self-reported pain is the main criterion used by clinicians assessing patients with pain. However, it is subjective, and multiple factors can affect pain levels. In this study, we investigated the neural correlates of FM pain using conditioned pain modulation (CPM), electroencephalography (EEG), and transcranial magnetic stimulation (TMS). Methods: In this cross-sectional neurophysiological analysis of a randomized, double-blind controlled trial, 36 patients with fibromyalgia were included. We analyzed CPM, EEG variables and TMS measures and their correlation with pain levels as measured by a visual analog scale. Univariate and multivariate linear regression analyses were performed to identify the predictors of pain severity. Results: We found: (1) no association between pain levels and CPM; (2) an association between reduced alpha and beta power over the central region in resting-EEG and higher pain levels; (3) an association between smaller event-related desynchronization (ERD) responses in theta and delta bands over the central region and higher pain levels; (4) an association between smaller ERD responses in theta and delta bands and smaller intracortical inhibition and higher intracortical facilitation ratios; (5) an association between smaller ERD responses in delta band and reduced CPM. Conclusions: Our results do not support CPM as a biomarker for pain intensity in FM. However, our specific EEG findings showing the relationship between pain, CPM and TMS measures suggest that FM leads to a disruption of inhibitory neural modulators and thus support CPM as a likely predictive marker of disrupted pain modulation system. These neurophysiological markers need to be further explored in potential future trials as to find novel targets for the treatment of FM.

Original languageEnglish
Pages (from-to)279-288
Number of pages10
JournalNeurophysiologie Clinique
Issue number4
StatePublished - Sep 2020


  • Biomarker
  • Chronic pain
  • Conditioned pain modulation
  • Electroencephalography
  • Event-related desynchronization
  • Fibromyalgia
  • Neural inhibitory state
  • Transcranial magnetic stimulation


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