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THE RELATIONSHIP BETWEEN THE MIGRAINE

AND OBSTRUCTIVE NASAL PATHOLOGIES
ARTICLE in ACTA MEDICA MEDITERRANEA JUNE 2014
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Acta Medica Mediterranea, 2014, 30: 1249

THE RELATIONSHIP BETWEEN THE MIGRAINE AND OBSTRUCTIVE NASAL PATHOLOGIES

EMRE GNBEY1, HAYRIYE KARABULUT2

1
Department of Otolaryngology, Ondokuz Mayis University, Faculty of Medicine, Samsun - 2Department of Otolaryngology, Gazi
University, Faculty of Medicine Ankara, Turkey

ABSTRACT
Objectives: Nasal obstruction may cause headache related with the sinusitis, mucosal contact points and accompanying symptom of snoring. Although migraine is a common disabling primary headache disorder, much about the cause of migraines isnt understood. The relationship of the obstructive nasal pathologies and migraine is not clear. The aim of this this study was to test the
hypothesis for migraine of sino-rhinogenic origin.
Methods: A prospective, randomized clinical study was conducted among 130 consecutive patients with migraine and 126
healthy control subjects at a tertiary medical center. The two groups were compared in terms of the obstructive nasal pathologies and
the correlation analysis between the grades and sides of pain and nasal pathologies are performed in the migraine group.
Results: The frequency (41/130, 17/126; p=0,006) and the grade (mean 1,9/0,9; p= 0,002) of the nasal septum deviation
(NSD) were significantly higher in migraine group than controls. There was also significant differences between the groups, in terms
of the frequency and the grade of inferior turbinate hypertrophy (ITH) (49/130, 25/126; p=0,01 and 1,2/0,8; p=0,03). There was a
significant correlation between the severity of pain and the grade of NSD and ITH (p=0,007; 0,004, respectively) There was no significant correlation between the side of obstructive nasal pathology and dominant side of the pain (p=0,889; p=0,567, respectively).
Conclusion: This study showed the increased obstructive nasal pathologies in patients with migraine. The patients who are clinically evaluated for migraine should receive comprehensive sino-rhinological examination.

Key words: Migraine, nasal obstruction, nasal septum deviation, turbinate hypertrophy.

Received February 18, 2014; Accepted June 19, 2014

Introduction
The imbalance of the nasal cavities associated
with nasal septal deviation (NSD) and and inferior
turbinate hypertrophies (ITH) is considered as a
common etiology of nasal airway obstruction.
Though the prevalence of NSD is as high as
22.38%, only 2.8% of the population with NSD
have nasal airway obstruction. Otherwise, NSD and
ITH constitute more than half of patients with nasal
obstruction(1-3). These deformities may cause chronic
mucosal irritation and reduction in nasal airflow
and may induce hypoxia and secondary mucosal
swelling in the paranasal sinuses. Nasal obstruction
leads to snoring, epistaxis, sinusitis, and various
upper airway infections(4).

Obstructive nasal pathologies may cause

headache related with the sinusitis, mucosal contact
points and accompanying symptom of snoring(5).
Migraine is a common disabling primary headache
disorder with the prevalence of 18.2% among
females and 6.5% among males in US(6). However,
the relationship of the obstructive nasal pathologies
and migraine is not clear.
We hypothesized that reduction in nasal airflow andmucosal irritation inpatients with obstructive nasal pathologies may influence the autonomic
nervous system activities and the paranasal sinus
nitric oxide levels. To test the hypothesis of rhinogenic origin for migraine, we performed endoscopic
nasal examination analysis of the migraine patients.

1250

Materials and methods

Study group
130 consecutive patients (69 females and 61
males; mean age 33 7 years) with a diagnosis of
classical type migraine (diagnosed in patients suffering from at least 15 headache days per month of
which at least eight are related to migraine) and 126
age-matched healthy control subjects (66 females
and 60 males; mean age 32 8 years) without
migraine were enrolled in the study after obtaining
informed consent(7). The diagnosis of migraine was
based on the criteria used by the International
Headache Society and was also supported by the
outcome and response to treatment after a mean of
6 months(7). No subject had obvious systemic disease. They had no smoking, alcohol and drug therapy. The existence of any possible systemic, maxillofacial and/or neurological disease which could
be the cuase of migraine have been exluded by
detailed anamnesis, neurological and otorhinolaryngological examination including nasal endoscopic
examination and laboratory and imaging studies if
necessary. Pain intensity of the patients with
migraine was classified from grade 1 to 3.
1: Mild, patient is aware of a headache, but
is able to continue daily routine with minimum
alterations.
2: Moderate, the headache inhibits daily activities, but is not incapacitating.
3: Severe, the headache is incapacitating)(7,8).
Also the sides of the pain were recorded. Patients
with concomitant disease such as allergic rhinitis,
nasal polyp and infection were excluded from the
study. Skin prick tests were performed for allergic
rhinitis. We also excluded patients who have a history of nasal surgery. The nasal endoscopic examination was done with 0 rigid endoscope. Nasal
septum deformities were evaluated by an otolaryngologist with according to Drehers(9) classification.
According to this classification, the relative degree
of the septum deviation was estimated and classified into four categories:
0 no deviation,
1 slight deviation,
2 moderate deviation,
3 severe deviation. The patients with third
degree (severe) septum deviation had chronic
mucosal contact.
The hypertrophy of the inferior turbinates was
classified from grade 0 to 2.
0: no hypertrophy;

Emre Gnbey, Hayriye Karabulut

1: slight hypertrophy;
2: severe hypertrophy)(9).
Alsothe sides ofthe detectedabnormalitieswere
recorded. Pathologies about middle turbinate,
nasopharynx and also the adenoid hypertrophies
were noted, if any.
Statistical analyses
Pearson correlation test and fisher's exact chisquare test were usedin statistical analysis.
Distribution of the continuous variables was determined by the KolmogorovSmirnov test.
Continuous variables with normal distribution were
expressed as mean SD; variables with skew distribution are expressed as median (minimum-maximum). All tests were found significant for p < 0.05.
Results
130 patients with migraine and 126 control
subjects were examined. Demographic data of the
migraine [mean age: 33 7; 69 (53%) females] and
control groups [mean age: 32 8 years; 66 (52%)
female] were similar (P = NS). No subjects had
chronic systemic disease.
According to the endoscopic nasal examination findings, the frequency (41/130, 17/126;
p=0,006) and grade (mean 1,9/0,9; p= 0,002) of the
NSD were significantly higher in migraine group
than controls. There was also significant differences between the groups in term of frequency and
grade of inferior turbinates hypertrophy (49/130,
25/126; p=0,01 for frequency and 1,2/0,8; p=0,03
for mean grades). Distributions are demonstrated
in Figure 1.

Figure 1: Box-plot graphics of the grade of NSD (a) and

ITH (b). The black lines within the boxes indicate the
median, the edges of the boxes are the 25th and 75th percentiles, and the lines extend to the maximum and minimum value.

The relationship between the migraine and obstructive nasal pathologies

There was a significant correlation between

the severity of pain and the grade of NSD and ITH.
However there was no significant correlation
between the side of obstructive nasal pathology and
dominant side of the pain. Pearson correlation
analyses are presented in table 1.
Pearson Correlation analyses in the migraine group
n=130

Grade of NSD

Grade of ITH

Pearson correlation

,001

,003

Sig. (2-tailed)

,007*

,004*

Side of NSD

Side of ITH

Pearson correlation

,557

,613

Sig. (2-tailed)

,889

,567

Intensity of pain

Side of pain

Table 1: The correlations between the grade and sides of

the pain and the grade and sides the of NSD and ITH.
(NSD: Nasal septum deviation, ITH: inferior turbinate
hypertrophy, * p<0,05, statistically significantvalues).

Discussion
This study showed that patients with migraine
had increased obstructive nasal pathologies. To the
best of our knowledge, this is the first study to
examine the relationship between the obstructive
nasal pathologies and migraine. NSD is a common
disorder causing nasal obstruction. The most common etiologies are nasal injury and irregular development of the nasomaxillary complex. ITH is an
another common obstructive nasal pathology. The
most common etiologies for ITH are allergy and
compensatory hypertrophy at the contralateral side
of NSD. These obstructive pathologies can lead to
chronic mucosal irritation, hypoxia in the paranasal
sinuses and sinusitis (3-11) . In obstructive nasal
pathologies, mucosal irritation is occurring by stimulation of afferent neurons of trigeminal nerve. The
sensory nerve supply of the nose arises from the
maxillary branch of the trigeminal nerve.
Sympathetic and parasympathetic fibers enter the
sphenopalatine ganglion from the deep petrosal
nerve. It may be a direct result of nerve fibers interacting with the chemical or an indirect result of
locally produced mediators(11,13).
Migraine is a common disabling primary
headache disorder. The goals of the treatment for
migraine are to decrease headache frequency,
headache severity and to avoid medication
overuse (12). Although much about the cause of
migraines isnt understood, genetics and environ-

1251

mental factors appear to play a role. Migraines may

be caused by changes in the brainstem and its interactions with the trigeminal nerve, a major pain
pathway. Sensory stimuli such as unusual smells,
including perfume, paint thinner, secondhand
smoke and others can trigger migraines in some
people.
In our study, we hypothesized that reduction in
nasal airflow andmucosal irritation resulting in
vagal stimulation inpatients with obstructive nasal
pathologies may also influence the autonomic nervous system activities and may effect the paranasal
sinus nitric oxide levels(13-15). Acar et al.(10) showed
the parasympathetic overactivity in patients with
NSD. Imbalances in brain chemicals which helps
regulate pain in the nervous system may be
involved. Researchers continue to study the role of
nitric oxide and serotonin in migraines (13-15). An
important issue in the generation of headaches is
mediation of neuropeptides, such as substance P.
These may be released by mechanical pressure
induced in areas of contacting opposing mucosal
surfaces, such as the nasal septum and the inferior
turbinate. Substance P can be liberated at both the
central and the peripheral ends of a sensory neuron,
mediating not only central pain reflexes, via afferent C fibers, but at the same time local reflexes at
the nasal mucosa, resulting from reverse impulses
and manifesting as vasodilation, extravasation of
plasma, hypersecretion, and smooth muscle contraction(17-19).
Stimulation of branches of the trigeminal
nerve induces a complex physiological response
carried on fibers innervating somatic receptors,
chemoreceptors, and baroreceptors(5,14,16,19). Daudia
et. (20) reported that twelve per cent of patients
attending a rhinology clinic with facial pain had
migraine and of particular interest were the 6% of
patients with facial pain who had migraine confined
to the second division of the trigeminal nerve.
However, they did not investigate the relationship
between the rhinologic pathologies and migraine.
Recently, Bandara(13) hypothesized that the diffused paranasal sinus nitric oxide in the nasal
mucosa could be the primary molecule that initiates
migraine and is termed Sinus hypoxic nitric oxide
theory. This hypothesis regards repetitive or intermittent activation of the trigeminal sensory nerve
and blood vessels in the nasal mucosa. Production
of paranasal sinus nitric oxide is mainly induced by
hypoxia due to several independent factors and the
diffusion of paranasal sinus nitric oxide depends on

1252

the vulnerable surface area in the nasal cavity.

Apart from the known trigeminal nociceptive
impulse in the migraine, two main peripheral
trigeminal nerve activating mechanisms may induce
migraine. First the nerve endings of the nasal
mucosa which are directly stimulated by diffused
paranasal sinus nitric oxide are indirectly stimulated by vasoactive substances released by antidromic
activation of the nerve, parasympathetic efferent of
the nerve and sterile neurogenic inflammation.
Secondly, the perivascular nerve of nasal mucosal
and the meningeal blood vessels are directly stimulated by either diffused paranasal sinus nitric oxide
or by shear stress mediation. The nerve impulses of
the trigeminal sensory nerve, projected at trigeminal nucleus caudalis to the central nerve system and
low plasma magnesium due to the consequence of
shear stress gives rise to the symptoms of migraine.
Moreover sino-rhinogenic impulses may mediate to
disruption of inhibitory sensitization modulated of
sensory input and cause sensory hyperexcitability.
In addition neuronal stimulation proposed by some
migraine hypotheses could also give rise to
migraine headache when the sino-rhinogenic vulnerable factors induce the migraine pathophysiology(5,13,14,16).
Our findings of increased obstructive nasal
pathology incidence of migraine patients, support
this new pathophysiological initiation between
sino-rhinogenic nitric oxide effects and migraine
and provides an initial step for the obscured or
neglected etiologically important neuro vascular
impulse generating pathway. In his letter Bandara(13)
concluded that, the patients who are clinically suspected of having headaches should receive comprehensive sino-rhinological examination and evaluation based on the sinus hypoxic nitric oxide theory.
A standard surgical and medical management of
migraine that links with the sinus hypoxic nitric
oxide theory may restore the hypoxic state or
reduce or remove the paranasal sinus nitric oxide
diffusing surface.
Our study is the first clinical testing of this
hypothesis. Our study showed that, the grade of
NSD and ITH effects the intensity of the pain in the
migraine patients. However there was no significant
correlation between the side of obstructive nasal
pathology and dominant side of the pain.
Stammberger and Wolf(18) reported that the cortical
center can not distinguish the original peripheral
source of the pain impulses and they may be misinterpreted as coming from other skin areas, such as

Emre Gnbey, Hayriye Karabulut

the temple, the zygoma or the forehead. The pain

may be perceived also from other endorgans innervated by terminal branches within the trigeminal
system, such as dura, intracranial and scalp vessels
or the eye(18,20).
Nasal obstructive pathologies can lead to snoring and/or obstructive sleep apnea syndrome.
Morning headache is common in habitual snorers
and associated with a pervasive impairment of
health-related quality of life. Migraines features are
not uncommon and not only OSAS, but migraine,
insomnia and psychological distress are also important predictors for morning headache, even in snoring patients. Chen et al(22) investigated the morning
headache in habitual snorers and they reported that
19% of the patients with morning headache fulfilled
the criteria for migraine attacks.
However, their study did not include the relationship between the level of obstruction and severity of the pain. Abu-Bakra et al.(5) reported that there
was no significant difference between the prevalence of nasal mucosal contact points of the patients
with facial pain compared with patients without
facial pain in their studies and they concluded that
surgery undertaken to remove mucosal contact
points for facial pain is usually unnecessary as the
etiology of this facial pain appears to be a more
central processes. Whereas, Perry et al.(23) reported
that migraine is the most common neurologic diagnosis (58%) in patients with nonrhinologic
headache in a tertiary rhinology practice. They did
not give the ratio of the migraine diagnosis for the
patients with rhinologic headache. It is important to
differ the migraine from the headaches caused by
acute or chronic rhinosinusitis, neuralgias,
otalgia,temporomandibular joint disease or vascular
head, midface discomfort(18).
Our study showed the increased obstructive
nasal pathologies in patients with migraine. Also a
significant correlation found, between the severity
of pain and the grade of obstruction. However,
there was no significant correlation between the
side of nasal obstruction and dominant side of the
pain. The patients who are clinically evaluated for
migraine should receive comprehensive sino-rhinological examination and evaluation based on the
sinus hypoxic nitric oxide theory.
Further clinical studies are needed, which
assess the changes inheadacheafter treatment of
nasal obstructions in the migraine patients.

The relationship between the migraine and obstructive nasal pathologies

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_________
Corresponding Author
EMRE GNBEY, M.D.
Ondokuz Mayis University, School of Medicine
Department of Otorhinolaryngology, Kurupelit,
Samsun, 55139
(Turkey)