Study: Restricted Sleep Increases Some Symptoms of Migraine

Using a transcranial magnetic stimulation method, researchers have found that reduced sleep alters central nervous inhibition from GABAergic and dopaminergic mechanisms differently in individuals with migraines versus those without.

Migraine is a primary headache disorder with a well-established association with insufficient sleep. According to the study, migraine affects approximately 15% of adults aged 15 to 64 globally and is the leading cause for years lived with disability below 50 years of age. Many patients with migraine report problems with sleep, headaches upon awakening, and using sleep as a way to avoid a headache. Researchers have also found worse sleep quality compared to individuals without migraines, as well as an increased likelihood for insomnia-like sleep patterns among individuals with migraines.

Sleep restriction with about 50% sleep for 2 nights is a human experimental model of insufficient sleep, according to researchers. In healthy subjects, sleep deprivation may alter cortical inhibitory and facilitatory systems, and seems to increase pain sensitivity. Increased sensitivity to pain has previously been discovered in patients with migraine and may be associated with both increased homeostatic sleep pressure caused by increased need for sleep as well as reduced intracortical inhibition.

Despite these findings, both the underlying pathophysiology of the disease and its relationship with sleep are unexplained. In order to investigate this association further, researchers applied transcranial magnetic stimulation to analyze possible mechanisms of insufficient sleep in patients with migraine.

A team of researchers used a randomized, blinded crossover design to examine 46 subjects with migraine during the interictal period and 29 healthy controls. The interictal period refers to the time between migraines, and each subject underwent recordings of cortical silent period, short- and long-interval intracortical inhibition, intracortical facilitation, and short-latency afferent inhibition after 2 nights of habitual 8-hour sleep and 2 nights of restricted 4-hour sleep.

All subjects were between the ages of 18 and 65 and were not allowed to use prophylactic treatment during the study period or at least 4 weeks before the first examination. Migraine subjects who have tension type headache for 7 days or more per month, or significant comorbid headache such as cluster headache or hypnic headache were excluded.

According to the analysis, sleep restriction had an opposite effect on cortical silent period duration in interictal migraines and controls. The cortical silent period refers to an interruption of voluntary muscle contraction by stimulating the contralateral motor cortex. With sleep restriction, this period was reduced from 147.9 minutes to 139.6 minutes. This impact was still significant when replacing sleep condition with measured sleep time in minutes.

More severe clinical symptoms were associated with shorter cortical silent period duration for several variables, including the frequency of migraines; severity of photophobia, phonophobia, and osmophobia; and premonitory yawning. No effects were found for usual attack duration, usual attack intensity, or years with headache.

Most notably, the researchers found a significant decrease in cortical silent period duration after sleep restriction in patients with interictal migraines compared to controls. This finding was more pronounced for patients with migraines with an aura and those with non-sleep related migraines, who typically do not have attacks during or at the end of sleep.

The reduced duration of the cortical silent period after sleep restriction is likely mediated by reduced inhibitor GABA-B activity and could potentially be modulated by both GABA-A activity and dopaminergic mechanisms related to wakefulness. In subgroup analyses, researchers found that reduced cortical silent period was demonstrated for migraines with an aura and for patients with non-sleep related migraine attacks. However, migraine subjects without aura displayed a different pattern of results and secondary analyses suggested a slightly altered GABA-A mediated inhibition after sleep restriction.

The investigators concluded that further research into distinct mechanisms between the subgroups may reveal implications of differentiated GABA or dopamine targeted treatment.

REFERENCE

Mykland M, Uglem M, Neverdahl J, Oie L, et al. Sleep restriction alters cortical inhibition in migraine: A transcranial magnetic stimulation study. Clinical Neurophysiology doi:10.1016/j/clinph.2022.04.004. https://www.sciencedirect.com/science/article/pii/S1388245722002383