| dc.description.abstract | Migraine is a common and debilitating primary headache disorder. Despite having pronounced personal, societal, and economical costs, the pathophysiology of migraine is not fully elucidated.
Migraine patients experience increased sensitivity to sensory stimuli between attacks. These symptoms may be caused by alterations in cortical excitability, inhibition, and/or facilitation. Alterations in cortical excitability could explain why migraine patients suffer spontaneous migraine attacks. Similarly, migraine patients may have increased pain perception and altered endogenous pain modulation between attacks. This could explain why migraine patients suffer recurring attacks of headache and cutaneous allodynia. Several studies have measured cortical excitability in migraine patients by using transcranial magnetic stimulation (TMS) on the motor cortex, and pain perception in migraine patients between attacks. However, studies have yielded discrepant results, which might be explained by different methodologies, such as lack of blinding.
Sleep disturbance is frequently reported as an attack trigger in migraine patients, and sleep disturbances increase the risk of developing migraine in healthy people. Investigating the effect of experimental sleep restriction on pain perception and endogenous pain modulation may provide insight into the basis for this relationship and the pathophysiology of migraine.
Methods
In the first study, we investigated motor cortical excitability using navigated TMS in 27 migraine patients in the interictal phase (between attacks), seven in the preictal phase (24 hours before an attack) and 33 healthy controls. In the second study, we compared warm detection threshold (WDT), pain thresholds, suprathreshold pain, temporal summation, and conditioned pain modulation (CPM) in 39 migraine patients between attacks and 31 healthy controls before and after experimental sleep restriction. In both studies, examiners were blinded to diagnosis, and in the second study, also to sleep condition.
Main results
We found that female migraine patients may have shortened cortical silent period (CSP), a measure of cortical inhibition. Additionally, migraine patients may have reduced shortinterval intracortical inhibition (SICI), a different measure of cortical inhibition, between attacks compared to controls. Shortened CSP and reduced SICI point to altered γ-aminobutyric acid (GABA)ergic inhibitory function. In study II, the effect of sleep restriction on pain perception was not significantly different between migraine patients between attacks and healthy controls in the primary analysis. However, we found that pressure pain thresholds (PPT) tended to be lower after sleep restriction in migraine patients between attacks when using a wider cut-off between the preictal and interictal phases. Additionally, heat pain thresholds (HPT) tended to be decreased after sleep restriction in sleep-related migraine. HPT was lower after sleep restriction in migraine patients with lower pain intensity during attacks. PPT was lower after sleep restriction in migraine patients with higher severity of photophobia during attacks. CPM, a measure of endogenous pain inhibitory mechanisms, tended to be more reduced after sleep restriction in migraine patients. CPM was reduced more after sleep restriction in sleep-related migraine, migraine patients with lower intensity of migraine headaches during attacks, and lower frequency of migraine headaches. In addition, we found that resting motor threshold (RMT) increased with sensitivity to sound during attacks, and lastly, we found decreased inhibitory, or increased facilitatory function in the period preceding a migraine attack (preictal phase), shown by increased intracortical facilitation (ICF).
Conclusions
Findings from the first study suggests altered inhibitory function in migraine patients between attacks. This alteration may be more pronounced in female migraine patients. Alterations in cortical inhibitory homeostatic mechanisms may render the migraine cortex susceptible to changes in cortical excitability. This could lead to the development of migraine attacks in response to certain triggers, such as stress, sleep disturbances, and sensory input. Subtly increased pain sensitivity in migraine patients between attacks could be caused by dysfunctioning pain modulatory mechanisms; sleep restriction may induce changes in an already subtly altered endogenous pain modulatory system in migraine, manifesting as slightly increased pain sensitivity. Increased pain sensitivity and altered endogenous pain modulation after sleep restriction between attacks could be specific to certain clinical subgroups, such as sleep-related migraine, and in migraine patients with lower headache intensity during attacks. Exploring the effects of sleep restriction in migraine could yield more knowledge about migraine neurophysiology, and why migraine patients are vulnerable to short-term disturbed sleep. More knowledge about clinical subgroups of migraine could lead to different therapeutic strategies in different subgroups. Proper blinding procedures are important for reliable results in migraine. | en_US |
