Meta-analytical evidence of functional and structural abnormalities associated with pain processing in migraine patients: An activation likelihood estimation

Medicine (Baltimore). 2022 Oct 28;101(43):e31206. doi: 10.1097/MD.0000000000031206.


Background: Migraine is a primary headache disorder that causes debilitating throbbing pain. Several functional MRI (fMRI) and voxel-based morphometry (VBM) studies have been used to investigate the structural and functional alteration in migraine. Here, we aim to study the converged brain regions of functional and structural abnormalities in gray matter volume (GMV) associated with pain processing and management in migraineurs and healthy controls (HC).

Methods: A systematic search through PubMed and Sleuth was carried out for peer-reviewed functional and structural neuroimaging studies on migraine patients and HC yielded a total of 1136 studies. We performed an activation likelihood estimation (ALE) meta-analysis on VBM and pain stimulation task-based fMRI studies to investigate the converged areas of GMV and functional abnormalities between migraineurs and HC. We performed two subgroup analyses between migraine with aura (MwA) and migraine without aura (MwoA) relative to HC, and between chronic migraine (CM) and episodic migraine (EM) compared to HC.

Results: The total sample included 16 fMRI and 22 VBM studies, consisting of 1295 migraine patients, compared to 995 HC. In fMRI analysis, ALE maps for pain stimulation tasks revealed hyperactivation in migraineurs in the substantia nigra compared to HC, whereas hypoactivation was seen in the cerebellum. For the VBM analysis, ALE clusters of increased GMV in migraineurs were observed in the parahippocampus and putamen nucleus. Whereas clusters of reduced GMV in migraineurs were seen in the frontal gyri. Compared to HC, MwoA patients showed a GMV reduction in the insula, and anterior cingulate, whereas MwA patients showed GMV reduction in the cerebellum, cingulate gyrus, and insula. CM patients showed decreased GMV in the precentral gyrus, whereas EM patients showed decreased GMV in the parahippocampus, and inferior frontal gyrus when compared to HC.

Conclusions: Our findings represent a potential biomarker for the diagnosis and management of migraine, by showing clustered brain regions of abnormal patterns of activation and GMV changes between migraineurs and HC which might be associated with hyposensitivity to pain in migraineurs. Further studies are required to determine disease progression or therapeutic interventions' effect on migraine.

Publication types

  • Meta-Analysis

MeSH terms

  • Brain / diagnostic imaging
  • Gray Matter
  • Humans
  • Likelihood Functions
  • Magnetic Resonance Imaging / methods
  • Migraine with Aura*
  • Migraine without Aura*
  • Pain / etiology