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Updated: Sep 13, 2025

Author Spotlight: Methodologies and Advancements of Chronic Pain Management Research
Published on: January 5, 2024
An ALE meta-analysis of pain processing alterations in fibromyalgia: Toward an evidence-based process model
Marco Cavicchioli1, Alberto Caruso2, Andrea Scalabrini3
1Department of Dynamic and Clinical Psychology, and Health Studies, Faculty of Medicine and Psychology SAPIENZA University of Rome, Rome, Italy; Faculty of Psychology, Sigmund Freud University, Milan, Italy.
Abstract:
It has been hypothesized that core pain-related symptoms of fibromyalgia (FM) might be associated with alterations of pain processing mechanisms. On the one hand, several fMRI studies were conducted to evaluate possible alterations of neural responsiveness toward the presentation of different kinds of noxious stimuli among patients with FM. On the other hand, a quantitative summary of these findings is still lacking. Accordingly, it was conducted an ALE meta-analysis (FWE, p < .05) of studies comparing brain responsiveness to the administration of painful stimuli between patients with FM and healthy controls (HCs). Twenty-one studies were included for meta-analytic procedures. Results showed 3 main findings: i) key areas of the pain matrix (i.e., dorsal anterior cingulate cortex [dACC], basal ganglia and thalamic nuclei) were commonly involved in pain processing in both FM patients and HCs; ii) pain processing in FM patients were characterized by a recruitment of the right insula; whereas, HCs mainly recruited prefrontal areas; iii) patients with FM, compared to HCs, showed an increased magnitude of dACC and supplementary motor area responsiveness toward the presentation of painful stimuli. These findings suggest that altered pain processing in FM is characterized by: i) an increased salience of painful stimuli, which are processed at a viscero-somatic non-mentalized level; ii) high intensity and low granularity of painful experiences accompanied by a negative valence, and modulated through maladaptive avoidance strategies; iii) the development of hypervigilance toward any potential harmful stimuli.
Insights
Fibromyalgia (FM) patients exhibit altered brain responses to pain, with increased activity in key pain processing areas like the dorsal anterior cingulate cortex (dACC). This suggests heightened pain sensitivity and vigilance in FM.
Area of Science:
- Neuroscience
- Medical Imaging
- Pain Research
Background:
- Core pain symptoms in fibromyalgia (FM) may stem from altered pain processing mechanisms.
- Functional magnetic resonance imaging (fMRI) studies have explored neural responsiveness to pain in FM patients, but a quantitative summary was lacking.
Purpose of the Study:
- To conduct an activation likelihood estimation (ALE) meta-analysis of fMRI studies comparing brain responsiveness to painful stimuli in FM patients versus healthy controls (HCs).
- To quantitatively summarize findings on neural alterations in pain processing in fibromyalgia.
Main Methods:
- ALE meta-analysis (FWE, p < 0.05) of 21 fMRI studies.
- Comparison of brain activation patterns between FM patients and HCs during painful stimuli presentation.
Main Results:
- Common recruitment of pain matrix areas (dACC, basal ganglia, thalamus) in both FM and HCs.
- FM patients showed increased recruitment of the right insula, while HCs recruited prefrontal areas.
- FM patients exhibited increased dACC and supplementary motor area responsiveness to painful stimuli compared to HCs.
Conclusions:
- Altered pain processing in FM involves increased salience of painful stimuli processed at a non-mentalized level.
- FM pain is characterized by high intensity, low granularity, negative valence, and maladaptive avoidance.
- Fibromyalgia is associated with the development of hypervigilance toward potentially harmful stimuli.

