Cortical plasticity in episodic and chronic cluster headache

• We identified gray matter (GM) changes in pain processing areas and beyond in patients suffering cluster headache (CH) compared to healthy controls
• GM changes significantly differed for different courses of the disease (chronic, episodic inside bout, episodic outside bout).
• GM decrease was predominantly observed in chronic CH, while episodic CH showed a more complex and partly opposite behavior.
• This dynamic probably reflects the brain's adaptation capacity to changing stimuli in regard to cortical plasticity and may provide an explanation of the diverse results of previous VBM studies in pain

Cluster headache (CH) is characterized by recurrent episodes of excruciatingly painful, unilateral headache attacks typically accompanied by trigeminal autonomic symptoms. Due to its rhythm with alternating episodes of pain and no-pain, it is an excellent model to investigate whether structural brain changes detected by magnetic resonance based voxel-based-morphometry (VBM) reflect the cause of the disease, may be a consequence of the underlying disease other than pain, or may simply be caused by the sensation of pain itself. We investigated 91 patients with CH in different stages of their disease using VBM and compared them to 78 age- and gender-matched healthy controls. We detected distinct regional gray matter (GM) changes in different brain regions including the temporal lobe, the hippocampus, the insular cortex and the cerebellum. The extent, location and direction of observed GM alterations depended on the state of disease and appeared dynamic in relation to pain state (i.e., pain vs. no-pain). No hypothalamic changes were detected in CH patients compared to healthy controls. The GM changes observed in this study are highly dynamic and thereby reflect the cortical plasticity of the brain in regard to pain. This observed dynamic may provide an explanation of the diverse results of previous VBM studies in pain. Regarding CH the results suggest that the disease is more likely to be caused by a network dysfunction rather than by a single malfunctioning structure.