Neurol Sci (2011) 32 (Suppl 1):S51–S54
DOI 10.1007/s10072-011-0524-5
MIGRAINE: PECULIAR CLINICAL AND THERAPEUTIC ASPECTS
Sleep and primary headaches
Marco Aguggia • M. Cavallini • N. Divito •
M. Ferrero • A. Lentini • V. Montano •
M. C. Tinebra • M. G. Saracco • W. Valfrè
Ó Springer-Verlag 2011
Abstract The relationship between sleep and primary
headaches has been known for over a century, particularly
for headaches occurring during the night or early morning.
Migraine, tension-tyre headache, and cluster headache may
cause sleep fragmentation, insomnia, and hypersomnia,
causing considerable social and economical costs and
several familial problems. By contrast, sleep disorders may
themselves trigger headache attacks. Finally, headaches
and sleep disorders can also be symptoms of other under-
lying pathologies. Despite this background, there is still no
clarity about the mechanism that links these two entities
and their interdependence remains to be defined. Patients
with primary headache should undergo a careful assess-
ment of sleep habits.
Keywords Sleep
Headache
Hypothalamus
Insomnia

Sleep apnea
Introduction
The deep relationship between headache and sleep has
been recognized for centuries and suspected intrinsically
related by anatomical and physiological aspects; even so
the exact nature of this association remains poorly under-
stood [1]. If from a side migraine attacks can be induced by
too little or prolonged sleep time, on the other hand
migraine crises can be reduced by sleep itself.
M. Aguggia (&)
M. Cavallini
N. Divito
M. Ferrero

A. Lentini
V. Montano
M. C. Tinebra

M. G. Saracco
W. Valfrè
Neurological Department, Cardinal Massaja Hospital,
Via Conte Verde 200, 14100 Asti, Italy
e-mail: aguggiamarco@tiscali.it
Several well-described primary headache disorders such
as migraine, cluster headache, and chronic paroxysmal
emicrania may occur mainly during either nocturnal or
diurnal sleep. Furthermore, hypnic headache syndrome
occurs typically during sleep [2]. However, headache and
sleeping disturbances remain both some of the most com-
monly reported problems in clinical practice, causing
considerable social, economical and familiar problems.
Patients with migraine, cluster headache and tension-type
headache are influenced by sleep stages, suggesting that
hypothalamus, in particular the suprachiasmatic nucleus,
may have a critical role in the pathogenetic relationship
between headache and sleep [3]. The involvement of
hypothalamic structures in the pathophysiology of primary
headaches is sustained by several studies, regarding mel-
atonin levels in migraine [4] and cluster headache [5].
Furthermore, low melatonin plasma levels were found in
sleepless patients affected by chronic migraine [6] and
melatonin supplementation itself seems to be effective in
the prophylactic treatment of cluster headache [7]. If so, a
timely recognition of sleep disorders in primary headache
patients is an essential step for identification, treatment,
and sometimes improvement of these pathologies [8]. Also
noradrenergic [9] and serotoninergic [10] pathways have
been claimed in the pathogenesis, taking into account the
great relief played by locus coeruleus and dorsal raphe
medianus in the management of the sleep–wake cycles and
in pain modulation.
Classification
The interrelation between sleep and headaches may pro-
ceed by several ways. This controversy is a still open
question and till date under discussion. The relationship
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between the two entities is complex, leading to various
models of potential interaction oriented to enhance our
understanding diagnosis and clinical management. Sahota
and Dexter [11] individualized the following types of
relations between headache and sleep: (a) sleep-related
headache (during or after sleep); (b) sleep phase-related
headaches (migraine and cluster headache); (c) length of
sleep and headaches and sleep relieves headaches
(migraine); (d) sleep disorders and headaches (sleep apnea,
parasomnia); (e) effects of headaches on sleep; (f) dreams
and headaches.
Possible clinical correlation between headache and sleep
has been stated by Paiva and Hering [12]: (a) sleep dis-
turbances are the cause of headache (i.e., morning head-
ache as a symptom of sleep apnea); (b) headache is the
cause of sleep disturbance (i.e., sleep disruption induced by
cluster headaches); (c) headache and sleep disorders may
overlap in the same subject or have a common cause (i.e.,
chronic tension headache and insomnia induced by mood
disorders). Furthermore Dodick and Parish [1] focused on
the overlap between the two entities, considered as ‘‘guilt
by association’’ and stated the following three paradigms:
(a) headache is the result of disrupted nocturnal sleep or the
underlying process that disrupts sleep (i.e., obstructive
sleep apnea or nocturnal hypoxia or hypercapnia, restless
leg syndrome or periodic leg movements of sleep, psy-
chophysiologic insomnia, chronic pain syndrome or fibro-
myalgia, depression or anxiety); (b) headache is the
‘‘causative disturb’’ of disturbance of nocturnal sleep (i.e.,
chronic tension-type headache, chronic migraine with or
without analgesic abuse or depression or anxiety);
(c) headache and sleep are intrinsically related by anatomy
and physiology (i.e., migraine, cluster headache, chronic
paroxysmal hemicrania, and hypnic headache). We must
remember that today all the hypotheses suggested in the
literature, turned to define a univocal model of interaction
between headache and sleep, is not fully shared.
Primary headache disorders and sleep
Migraine
Migraine is a recurring primary unilateral headache that
occurs one or more times per month and can last 4–72 h.
More commonly reported in females, typical pain is one-
sided, pulsating, described as pounding or throbbing, of
moderate to incapacitating severity, aggravated by physical
activity and associated with nausea and/or vomiting, photo
and phonophobia. Migraine can be associated with tran-
sient neurological symptoms, and in 15–20% of patients,
aura usually precedes the headache with visual or sensory
deficits [13]. Attacks are frequently triggered by several
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Neurol Sci (2011) 32 (Suppl 1):S51–S54
factors, supporting his cyclic nature and an hypothalamic
involvement. Biorhythm alterations (hormonal changes,
sleep–wake cycles, sleep stages, lack or excess of sleep,
and sideman work), geoclimatic factors (seasonal varia-
tions and temperature and barometric shifts, light–dark
cycle), emotional change, affective mutations, and changes
in daily routine (meal times, work and rest cycle, holidays
and week end) may play a crucial role for migraine attacks
[14]. Primary headache disorders often occur during sleep
and, therefore, may be strictly associated with the patho-
physiology of sleep itself. Sleep pattern may be involved in
the precipitation of migraine attacks, that can occur during
nocturnal sleep, after brief period of daytime sleep, and
overall on awakening [15]. The rapid eye movement
(REM) sleep represents the sleep phase typically more
concerned in migraine attacks, while morning arousal is
associated with stage III and IV and REM sleep itself.
Polysomnography studies in migraneurs have shown a link
between the beginning of nocturnal sleep, headache and
REM periods [16]. Moreover, sleep has also been shown to
relieve migraine, especially in children [17].
Short sleepers showed a greater tendency to develop
migraine attacks during nocturnal sleep and were also more
prone to show awakening headache [18]. Furthermore, an
excessive daytime sleepiness can be found in migraine
patients. [19].
An unpleasant physical phenomena that can occur dur-
ing sleep at night, known as parasomnias, have been found
more frequently in migraine patients compared with con-
trols. So sleepwalking, nocturnal enuresis, and pavor noc-
turnus, may more often occur in this population [20].
Tension-type headache
Previously called tension headache, muscle contraction
headache, psychomyogenic headache and stress headache,
was finally classified by The International Headache
Society as tension-type headache (TTH). Attacks can last
from 30 min to 7 days, and the limit of 15 days of head-
ache per month divides the episodic from the chronic form,
that usually persists for more than 6 months. Just the
chronic form is often associated with severe pain combined
with medication overuse. Typically, pain is bilateral, with
oppressive quality and ranging from moderate-to-mild
intensity [13]. This primary headache may be associated
with sleep disturbances such as insomnia, hypersomnia and
circadian disturbances. Moreover, many of these patients
are comorbid not only with anxiety and depression but also
with chronic pain [21]. TTH patients have a reduced
amount of global nocturnal sleep, decreased efficiency and
quality of rest periods, reduced sleep latency, early and
frequent awakenings with a global reduction of slow wave
sleep stages, without change in REM periods. Sleep
Neurol Sci (2011) 32 (Suppl 1):S51–S54
disorders in patients with detectable tensive chronic head-
aches and headaches associated with analgesic abuse are
very similar to those of patients with depression, dysthy-
mia, musculoskeletal disorders, fibromyalgia and pain. The
profiles of sleep are characterized by their global reduction,
reduced efficiency and for a decrease in slow stages of
sleep; by contrast, frequent awakenings are observed
simultaneously with an increase of involuntary movements
at night [22].
Cluster headache
Cluster headache (CH) is a debilitating primary headache
characterized by unilateral conjunctival injection, rhinor-
rhea, and lacrimation with severe retro or periorbital pain.
Attacks in the episodic form (ranging 80% of the patients)
lasts 1 week to 1 year alternating with free-pain interval
while there is no pain remission in the chronic form. CH
occurs predominantly in man, especially if heavy smokers
and may be precipitated by several factors such as nitro-
glycerine, alcohol abuse, irregularity of sleep, environ-
mental alterations, and change in the level of physical,
emotional, or mental activity [13, 23]. There is strong
evidence supporting a relationship between CH, sleep and
the ‘‘biological clock’’ and experimental evidences support
the hypothalamic involvement [24]. For years have been
described alterations in the circadian rhythm of several
hormones secretion, such as melatonin, cortisol, growth
hormone, testosterone, thyrotropin, and prolactin [25].
Considering these observations, it is not surprising that CH
attacks often occur at the same hour each day with char-
acteristic peak times. The association between CH and
sleep has been long recognized for its typical critical onset
during nocturnal sleep. Generally, the crisis began about
90 min after sleep onset, a period that coincides with the
beginning of the first REM phase [26]. However, there are
reports which have found an association between REM
sleep and attack only in the chronic forms [27]. Transient
insomnia is linked to the critical period, and it tends to
withdraw with the subside of the cluster itself [28]. It was
also hypothesized a relationship between CH and nocturnal
breathing disorders, given the onset of the crisis during the
night and the response to oxygen therapy during the acute
attack. If seems reasonable to assume that nocturnal
breathing disorders may cause CH, they certainly worsen
the attacks. On this matter large population studies and for
long observational periods are expected [29].
Hypnic headache
Hypnic headache (HH) is a rare benign syndrome, with
recurrent attacks occurring exclusively during night–time
sleep or daytime nap, in subjects older than 60 years. The
S53
original description was made by Raskin in 1988 [30] and
is included in IHS Classification [13]. HH can be rightly
considered as the better correlation between headache and
sleep, usually occurring with striking consistency the same
time every night. A moderate–severe pain that lasts from
15 min to 3 h, which can be repeated up to four times a
night, defines the clinical pattern. The original hypothesis
of Raskin closely correlated the attacks to the REM fase of
sleep, perhaps due to a dysregulation of the hypothalamic
pacemaker; later there have been reports in support of this
hypothesis through polysomnographic studies [30]. HH
may, therefore, be a correlated-REM phenomenon, and a
nocturnal fall in oxygen saturation would be responsible
for headache in predisposed subjects. It seems reasonable
to consider the HH a disorder related to the sleep physi-
ology and with its changes during aging [1]. However, it
must be remembered that till date there is no agreement to
support a safe and incontrovertible link between the attacks
and nocturnal desaturation.
Sleep disorders
Insomnia
Insomnia is the most common sleep abnormality seen in
adults, defined by ‘‘a repeated difficulty with sleep initia-
tion, duration, consolidation or quality that occurs despite
adequate time and opportunity for sleep and results in some
form of daytime impairment’’ [31]. Although the mecha-
nism is not fully understood, the sleepless are more likely
to have headache than healthy subjects. The characteristic
pattern of this headache, probably related to changes in the
architecture of sleep, closely recalls the tension-type
headache, although the typical profile has not yet been
defined [9]. It must be emphasized that insomnia is fre-
quently comorbid with somatic and psychiatric disorders
such as depression, anxiety, myalgia, muscle tension, and
fibromyalgia [22, 32]. Future studies will be able to better
clarify the relationship between insomnia and mood
disorders.
Sleep apnea
Headache one of the cardinal symptoms of obstructive
sleep apnea syndrome (OSAS) varies widely in frequency,
ranging from 15 to 50% [33, 34]. Patients with OSAS
frequently have excessive daytime sleepiness, chronic
fatigue, morning headache, snoring, and nocturnal arousals.
Hypoxia, hypercapnia, arousals, and sleep disruptions are
present during OSAS, resulting in alterations of blood
pressure control mechanisms, ventilatory disregulation,
vascular alterations, and increased sympathetic tone [35].
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Then, it is not surprising that these patients may suffer
from an awakening headache, compared with both normal
subjects and patients with other sleep disturbances [36].
The reported headache is a tension-type headache although
no attempts to further classification have been made and its
occurrence and severity seems to be associated with
intensity of OSA [37]. Moreover, OSAS may frequently
occur in CH patients [23] while there are currently insuf-
ficient data related to migraine [20] Being so, the correla-
tion between sleep apnea and morning headache is not fully
understood and remains controversial, although several
hypotheses have been proposed to clarify the relationship
between OSAS and the headache at awakening. Above all
the fluctuation of oxygen saturation and hypercapnia dur-
ing the night sleep can increase the intracranial pressure.
The putative mechanisms are complex and further data are
required [38].
Conflict of interest The authors declare that there is no actual or
potential conflict of interest in relation to this article.
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