Rhythmicity in primary headache disorders

Chronobiology plays a major role in primary headache disorders, Dr Christoph Schankin (University Hospital of Bern, Switzerland) argued in a lecture on the relationship between headache and the biological clock [1]. The hypothalamus is a key structure for rhythm generation and pain modulation. Medication altering rhythmicity might be helpful as treatment.

Dr Schankin explained that circadian rhythm is present at single-cell level, and that organs function together as a single circadian unit (the peripheral clock). They run independently and are synchronised by a central ‘pacemaker’, the suprachiasmatic nucleus (SCN). The SCN is calibrated by ‘Zeitgeber’: light, food, temperature, exercise, and circadian hormones (most notably steroids, melatonin). Steroids and melatonin not only change the SCN, but are also changed by it.

There is clinical evidence of circadian rhythmicity in migraine and other primary headache disorders: most attacks start between noon and 1 PM. Furthermore, ‘early risers’ in general have migraine attacks that start early in the day. Cluster headache mostly seems to start very early in the morning: at 1 or 2 AM. There is also a possible circaceptan (weekly) rhythmicity in migraine, with more attacks on Fridays and fewer on Sundays. Women often have migraine attacks at the beginning of the menstrual period. Migraine attacks seem to originate in the subcortical areas, and/or from the hypothalamus, as was confirmed in imaging studies. There is a clear circannual rhythmicity in cluster headache, which can be provoked by very long and short days (in June and December, respectively). Other patients have relatively very few attacks in summer.

It is unclear which factors drive rhythmicity in migraine and other primary headache disorders. There is evidence for involvement of the hypothalamus and its major mediators (CLOCK, CK1, PACAP, melatonin, orexins). The association with sleep is bidirectional: sleep is affected by headache, and headache by sleep.

Dr Schankin said medication altering rhythmicity may be helpful as migraine treatment. Among the interventions that have been studied thus far are melatonin and corticosteroids (to reset the body clock), orexin A and B (involved in sleep, arousal, feeding), lithium and valproic acid, and PACAP. Solid evidence for any of these options is still lacking.

1. Schankin C. Rhythmicity in Headache Disorders. SYMP10-2, EAN 2021 Virtual Congress, 19–22 June.

 

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Posted on 18 August 202118 August 2021