Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI

Objectives: The aim of the present study was to systematically review the literature addressing pain-induced changes in the brain related to central sensitization in patients with fibromyalgia (FM) using specific functional (rs-fMRI and fMRI) and structural (voxel-based morphometry-VBM) brain MRI techniques.

Methods: PubMed and Web of Science were searched for relevant literature using different key word combinations related to FM, brain MRI, and central sensitization. Full-text reports fulfilling the inclusion criteria were assessed on risk of bias and reviewed by two independent reviewers.

Results: From the 61 articles that were identified, 22 met the inclusion criteria and achieved sufficient methodological quality. Overall, eight articles examined structural brain (VBM) changes in patients with FM, showing moderate evidence that central sensitization is correlated with gray matter volume decrease in specific brain regions (mainly anterior cingulate cortex and prefrontal cortex). However, global gray matter volume remains unchanged. A total of 13 articles evaluated brain activity (fMRI) in response to a nociceptive stimulus. Findings suggest a higher but similar pattern of activation of the pain matrix in FM patients compared to controls. There is also evidence of decreased functional connectivity in the descending pain-modulating system in FM patients. Overall, two articles examined intrinsic brain connectivity in FM patients with rs-fMRI. In conclusion, there is moderate evidence for a significant imbalance of the connectivity within the pain network during rest in patients with FM.

Conclusions: The included studies showed a moderate evidence for region-specific changes in gray matter volume, a decreased functional connectivity in the descending pain-modulating system, and an increased activity in the pain matrix related to central sensitization. More research is needed to evaluate the cause-effect relationship.