Cortical plasticity between the pain and pain-free phases in patients with episodic tension-type headache

BACKGROUND: State-related brain structural alterations in patients with episodic tension-type headache (ETTH) are unclear. We aimed to conduct a longitudinal study to explore dynamic gray matter (GM) changes between the pain and pain-free phases in ETTH. METHODS: We recruited 40 treatment-naïve ETTH patients and 40 healthy controls. All participants underwent brain structural scans on a 3.0-T MRI system. ETTH patients were scanned in and out of pain phases. Voxel-based morphometry analysis was used to determine the differences in regional gray matter density (GMD) between groups. Additional regression analysis was used to identify any associations between regional GMD and clinical symptoms. RESULTS: ETTH patients exhibited reduced GMD in the bilateral primary somatosensory cortex, and increased GMD in the bilateral anterior cingulate cortex (ACC) and anterior insula for the in pain phase compared with the out of pain phase. The out of pain phase of ETTH patients exhibited no regions with higher or lower GMD compared with healthy controls. GMD in the left ACC and left anterior insula was negatively correlated with headache days. GMD in the left ACC was negatively correlated with anxiety and depressive symptoms in ETTH patients. CONCLUSIONS: This is the first study to demonstrate dynamic and reversible GMD changes between the pain and pain-free phases in ETTH patients. However, this balance might be disrupted by increased headache days and progressive anxiety and depressive symptoms.