Yawning is considered to be a symptom that
reflects dopaminergic activity, although its
pathophysiological mechanism is not yet fully
understood. Interestingly, repetitive yawning is
seen in some patients during migraine attacks.
The aim of this cross-sectional study is to
investigate the frequency of yawning during
migraine attacks and its association with
different characteristics of migraine.
Patients with migraine with or without aura
were evaluated using questionnaires and diaries
to determine the characteristics of headache and
accompanying symptoms. Repetitive yawning in the
premonitory phase and/or during headache were
determined.
Three hundred and thirty-nine patients were
included in the study. One hundred and
fifty-four patients reported repetitive yawning
(45.4%) during migraine attacks. Repetitive
yawning was reported in the 11.2% of the
patients in the premonitory phase, 24.2% during
headaches, and 10% both in the premonitory phase
and during headaches. Migraine with aura (46.8
vs 31.9%; P5.005), accompanying nausea (89.6 vs
75.1%; P5.001), vomiting (48.7 vs 37.8%;
P5.044), osmophobia (66.7 vs 52.3%; P5.024), and
cutaneous allodynia (58.2 vs 46%; P5.032) were
more common in patients with yawning than
without. Other dopaminergic-hypothalamic
premonitory symptoms (41.6 vs 26.5%; P5.003),
especially sleepiness (17.5 vs 5.9%; P5.001),
irritability/anxiety (21.4% vs 11.4%; P5.019),
nausea/vomiting (10.4 vs 4.3%; P5.03), and
changes in appetite (18.2 vs 9.7%; P5.024), were
also more frequent in patients with yawning than
without. After being adjusted for all other
relevant covariates, the odds of repetitive
yawning were increased by the presence of nausea
(OR 2.88; 95% CI 1.453-5.726; P5.002) and
migraine with aura (OR 1.66; 95% CI 1.035-2.671;
P5.036).
These results demonstrated that yawning is a
common self-reported symptom leading or
accompanying migraine attacks and is associated
with aura, nausea and/or vomiting, osmophobia,
and cutaneous allodynia in patients with
migraine. Although yawning is a rather
frequently seen behavior, it is a unique and
reliable symptom in patients with migraine that
may offer an opportunity for early treatment of
migraine attacks.
Résumé
Le bâillement est
considéré comme un symptôme
qui reflète l'activité
dopaminergique, bien que son mécanisme
physiopathologique ne soit pas encore
entièrement compris. Fait
intéressant, des bâillements
répétitifs sont observés
chez certains patients lors d'attaques de
migraine. Le but de cette étude
transversale est d'étudier la
fréquence des bâillements lors des
crises de migraine et son association avec
différentes caractéristiques de la
migraine.
Les patients atteints de migraine avec ou
sans aura ont été
évalués à l'aide de
questionnaires et d'auto-observations afin de
déterminer les caractéristiques du
mal de tête et des symptômes qui
l'accompagnent. Les bâillements
répétitifs à la phase
prémonitoire et / ou pendant le mal de
tête ont été
analysés.
Trois cent trente-neuf patients ont
été inclus dans l'étude.
Cent cinquante-quatre patients ont
signalé des bâillements
répétitifs (45,4%) lors d'attaques
de migraine. Des bâillements
répétés ont
été rapportés chez 11,2%
des patients en phase prémonitoire, 24,2%
lors des maux de tête et 10% à la
fois dans la phase prémonitoire et
pendant les maux de tête.
La migraine avec aura (46,8 vs 31,9%,
P5.005), c'est à dire accompagnée
de nausées (89,6 vs 75,1%, P5.001), de
vomissements (48,7 vs 37,8%, P5,044),
d'osmophobie (66,7 vs 52,3%, et l'allodynie
cutanée (58,2 vs 46%, P5.032)
était plus fréquente chez les
patients ayant des bâillements que chez
ceux sans. Autres symptômes
prémonitoires dopaminergiques et
hypothalamiques (41,6 vs 26,5%, P5.003), en
particulier la somnolence (17,5 vs 5,9%;
P5.001); l'irritabilité /
l'anxiété (21,4% vs 11,4%;
P5,019); les nausées / vomissements vs
4,3%, P5,03), et les changements
d'appétit (18,2 vs 9,7%; P5.024)
étaient également plus
fréquents chez les patients avec
bâillements que sans.
Après ajustement pour toutes les
autres covariables pertinentes, les risques de
bâillements répétitifs ont
été augmentés en cas de
nausées (OR 2,88, IC 95% 1,453-5,726,
P5,002) et de migraine avec aura (OR 1,66; IC
95% 1,035-2,671 ; P5.036).
Ces résultats montrent que le
bâillement est un symptôme commun
auto-déclaré débutant ou
accompagnant les crises de migraine et est
associé à une aura, des
nausées et / ou des vomissements, une
osmophobie et une allodynie cutanée chez
des patients souffrant de migraine. Bien que le
bâillement soit un comportement
fréquemment observé, il s'agit
d'un symptôme unique et fiable chez les
patients souffrant de migraine qui peut offrir
une opportunité de traitement
précoce des crises de migraine.
The variety of symptoms developed during
migraine attacks indicates that different parts
of the brain are affected directly or
indirectly. The symptoms that start from the
premonitory phase, accompany headaches during
attack, and extend to the postdromal phase
reflect a wide range of neural system
dysfunction. In addition, findings such as
hypersensitivity to visual, auditory, and
olfactory stimuli seen in migraine patients
during the interictal period may be included in
this scope.
Prevalence of premonitory symptoms of
migraine patients varies between 7% and 88%,
depending on the study population and design.
The most common symptoms in the premonitory
phase indicate the possible influence of the
hypothalamus, brainstem, cortex, and the limbic
system.
Yawning is a phylogenetically old,
stereotypic behavior seen in most mammals
ranging from rodents to humans.The role of
yawning in human physiology is not yet fully
understood. There are numerous descriptions and
explanations of yawning: some state that it
increases wakefulness and aims to make a person
more alert when they feel sleepy; some state
that it is a thermoregulatory mechanism, which
may be triggered by an increase in heat of the
brain and provide compensatory cooling when the
other options fail; and some state that it has a
respiratory function to regulate oxygen and
carbon dioxide levels in the blood.
However, yawning is considered to have a
significant role in providing social and
empathetic communication. Although the
physiological role of yawning has not been fully
elucidated yet, studies conducted over the past
50 years have provided a better understanding of
the neuropharmacological regulation of yawning.
Many neurotransmitters and neuropeptides,
especially dopamine and oxytocin as well as
acetylcholine, glutamate, serotonin,
gammaaminobutyric acid, opioids, adrenergic,
nitric oxide, gonadal hormones, and orexin were
found to be responsible for the modulation of
yawning.
Paraventricular nucleus of hypothalamus
plays a key role in the occurrence of yawning.
The stimulation of dopamine D2 receptors of the
nucleus activates oxytocinergic neurons
projected to the pons (reticular formation,
locus coeruleus), hippocampus, insula, and
orbitofrontal cortex. Oxytocin stimulates
cholinergic transmission in the hippocampus, and
acetylcholine ultimately causes yawning through
muscarinic receptors of the effectors.
Excessive yawning is seen in several
neurological disorders such as vasovagal
syncope, migraine, intracranial hypertension,
epilepsy, pituitary tumors, and stroke.
Iatrogenic yawning may develop due to the use of
dopaminergic medication and serotonin reuptake
inhibitors.
In this study, we aimed to determine the
frequency of yawning accompanying migraine
attacks and to investigate the relationship
between yawning and the clinical features of
migraine.
DISCUSSION
In this study, repetitive yawning was
reported in 45% of patients during migraine
attacks. Most of the studies investigating the
frequency of premonitory symptoms in migraine
attacks reported the frequency of yawning
between 34 and 40%;4-6 however, some studies
reported lower frequencies. Yawning was
evaluated as a premonitory symptom in most of
the previous studies. The frequency of
accompanying symptoms in the premonitory, ictal,
and postdromal phases of migraine attack was
investigated in only one study, and was reported
that yawning during headaches is seen to a
similar extent as in the premonitory phase, and
27.8% of the patients reported yawning in the
premonitory phase, 25.4% during headache, and
13.9% in the postdromal phase.3 In our study,
repetitive yawning was not only reported in the
premonitory phase but also even more frequently
during headache, and it was reported both in the
premonitory phase and during headache in some of
the patients. These findings can be explained
since the activation of
dopaminergic-hypothalamic mechanisms causing
yawning in migraine attack exists during both
the premonitory phase and during headache. In
addition, there is a similarity between yawning
and symptoms such as nausea, vomiting, and
photosensitivity and phonosensitivity, since
these symptoms can be seen both in the
premonitory phase and during headache.
Repetitive yawning is important as a symptom
because it can be evaluated more objectively by
the patients with migraine when compared with
other frequently seen symptoms in the
population, such as fatigue or depressive mood
state. It was reported that yawning can predict
the onset of headache in 84% of cases and was
suggested to be one of the most predictive
premonitory symptoms.3 We observed that the
patients were responding without any doubt when
we asked them if they had yawning before or
during headache compared to other symptoms.
The hypothalamus plays an important role in
the human circadian rhythm and in the
maintenance of homeostasis. Since brains with
migraines are highly sensitive to changes in
homeostasis, it is possible that the
hypothalamic neurons are the source of
dopamine-mediated premonitory symptoms, such as
yawning.1,2 In a study carried out using H15 2
O-PET in patients with nitroglycerintriggered
migraine attacks, activations in the
posterolateral hypothalamus, midbrain tegmental
area, periaqueductal gray, dorsal pons, and
various cortical areas including occipital,
temporal, and prefrontal cortex were observed in
the premonitory phase of headache.8 Considering
the known pain modulatory effects of these
areas, it was suggested that the early
activation of these areas before headache may
represent an abnormal response, resulting in
increased pain.
In this study, migraine with aura was found
to be more frequent in patients with repetitive
yawning than without. Migraine aura is known to
develop as a result of cortical spreading
depression. However, the specific event
initiating the cortical spreading depression is
unknown. The threshold for initiation of
cortical spreading depression is probably lower
in patients with migraine with aura compared to
healthy individuals and might be associated with
hyperexcitability of the brain. The timing of
aura relative to premonitory symptoms of
migraine raises the question about its role in
initiating headache. Factors initiating aura and
premonitory symptoms of migraine attack may be
common and explain the relation between aura and
yawning in our study. It was suggested that
ongoing neurophysiologic abnormalities during
the pain-free interval may lead to both
premonitory symptoms and create the conditions
for ignition of cortical spreading
depression.
Reciprocal anatomic connections between the
hypothalamus and spinal trigeminal nucleus have
been demonstrated. Findings demonstrating the
activation of hypothalamic areas during migraine
indicated its role in pain modulation and
contribution to the development of central
sensitization in trigeminovascular neurons. It
was supported by a study demonstrating that the
paraventricular hypothalamic nucleus neurons
directly control both spontaneous and induced
activities of spinal trigeminovascular neurons
in rats. These findings may explain the
association between yawning and allodynia, which
reflects central sensitization in our
study.
In this study, nausea and vomiting were
found to be more frequent both in the
premonitory phase and during headache in
patients with repetitive yawning during migraine
attacks. This relationship may be interpreted to
suggest that nausea and vomiting also reflect
increased dopaminergic activity, as in yawning.
Although functional connections between
trigeminal neurons and nucleus tractus
solitarius may explain the presence of nausea
along with headache, nausea&emdash;which is also
seen as a premonitory symptom&emdash;is thought
to be a centrally developed symptom in migraine.
The results of a study using H15 2 O PET in the
premonitory phase of a migraine attack triggered
by nitroglycerin showed that nausea may develop
independently of pain and trigeminal activation.
In addition, connections between paraventricular
nucleus of hypothalamus and nucleus tractus
solitarius and area postrema demonstrate the
role of the hypothalamus in development of
nausea and vomiting. In our study, osmophobia,
which reflects dopaminergic neurotransmission,
was also found to be more frequent in patients
with repetitive yawning than without. This study
showed that the number of patients with other
dopaminergic-hypothalamic premonitory symptoms
is higher in patients with repetitive yawning
than without. Sleepiness was found to be more
frequent in patients with yawning, and it may be
associated with the role of the hypothalamus in
the sleep-wake cycle. However, the physiological
function of yawning to increase alertness is
also thought to contribute to the association of
these two symptoms.
This study has some limitations. First,
estimating the frequency of repetitive yawning
or other symptoms was based on self-reported
data obtained from the patients. As data were
obtained from selfreported questionnaires or
diaries, underestimation might have occurred due
to not recalling the premonitory and associated
yawning. Overestimation might have occurred due
to having affirmative responses when study
participants were asked if they had any
repetitive yawning associated with headache. We
cannot discount the possibility that there might
still be incorrect or inadequate responses in
the questionnaires or diaries, although of the
patients were excluded from the study due to the
fact that they had failed to complete the
questionnaires or had unreliable responses.
Furthermore, some patients might have had
difficulties in distinguishing the time of
yawning prior to an accompanying headache.
Second, our study did not assess the
prophylactic medications for migraine. It is
known that antidepressant drugs may induce
yawning, but both groups of patients with or
without yawning had used these drugs similarly
(21.4 vs 23.8%). Finally, we used multiple
logistic regression analysis to determine the
variables which may have an effect on yawning,
but no adjustment for multiple comparisons was
done in this study.
CONCLUSIONS
This study demonstrated that yawning is a
common symptom that leads to or accompanies
migraine headache and indicated an association
between yawning and aura, nausea and/or
vomiting, osmophobia, and cutaneous allodynia in
patients with migraine. Yawning is a unique and
objective symptom that may offer an opportunity
for early treatment of migraine attacks.
