Abstract
Patients’ accounts of cluster headache attacks, ictal restlessness, and electrophysiological studies suggest that the pathophysiology involves Aδ-fibre nociceptors and the network processing their input. Continuous activity of the trigeminal autonomic reflex throughout the in-bout period results in central sensitization of these networks in many patients. It is likely that several factors force circadian rhythmicity upon the disease. In addition to sensitization, circadian changes in pain perception and autonomic innervation might influence the excitability of the trigeminal cervical complex. Summation of several factors influencing pain perception might render neurons vulnerable to spontaneous depolarization, particularly at the beginning of rapid drops of the pain threshold (“summation headache”). In light of studies suggesting an impairment of short-term synaptic plasticity in CH patients, we suggest that the physiologic basis of CH attacks might be network overactivity—similarly to epileptic seizures. Case reports documenting cluster-like attacks support the idea of distinct factors being transiently able to induce attacks and being relevant in the pathophysiology of the disorder. A sustained and recurring proneness to attacks likely requires changes in the activity of other structures among which the hypothalamus is the most probable candidate.
Highlights
Patients’ accounts of Cluster headache (CH) attacks, ictal restlessness, and some electrophysiological studies suggest that the pathophysiology of CH involves Aδ-fibre nociceptors and networks processing their input
Continuous activity of the trigeminal autonomic reflex throughout the in-bout period might result in central sensitization within these networks in many patients
It seems possible that an interplay of several factors allows for spontaneous depolarization and forces circadian rhythmicity upon the disease
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. But not randomly—the time of day, as well as age and sex, modulate the probability of their occurrence [5–7]. To understand the origin of the pain, researchers used imaging techniques—positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)—to track brain activity during the attacks [8,9]. They did not identify an attack generator but documented increased activity in the posterior hypothalamus, thalamus, insular cortex, as well as anterior cingulate cortex. [10] and the time of day as well as age and sex, are influencing factors, too [11–18].
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