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Reduced gray matter volume was found in frontal pain-modulation areas in patients with cluster headache, suggesting the involvement of insufficient pain-modulating capacity in this disorder.Previous functional imaging studies in episodic cluster headache (CH) patients revealed altered brain metabolism concentrated on the central descending pain control system. However, it remains unclear whether changes in brain metabolism during the “in bout” period are due to structural changes and whether these structural changes vary between the “in bout” and “out of bout” periods. To quantify brain structural changes in CH patients, the regional gray matter volume (GMV) was compared among 49 episodic CH patients during the “in bout” period and 49 age- and sex-matched controls. Twelve patients were rescanned during the “out of bout” period to evaluate the changes, if any, between these 2 periods. Compared with healthy controls, CH patients showed significant “in bout” GMV reductions in the bilateral middle frontal, left superior, and medial frontal gyri. Compared to “out of bout” scans, the “in bout” scans revealed significant GMV increases in the left anterior cingulate, insula, and fusiform gyrus. Additionally, compared to healthy controls, the “out of bout” scans revealed a trend of GMV reduction in the left middle frontal gyrus. These affected regions primarily belong to frontal pain modulation areas, and thus these GMV changes may reflect insufficient pain-modulating capacity in the frontal areas of CH patients.