Pain Medicine 2015; 16: 1629–1634
Wiley Periodicals, Inc.
HEADACHE & FACIAL PAIN SECTION
Original Research Article
Generalized Pressure Pain Hypersensitivity in
the Cervical Muscles in Women with Migraine
Lidiane Lima Florencio, MD,*
Maria Carolina Merli Giantomassi,*
Gabriela Ferreira Carvalho, MD,*
Maria Claudia Gonçalves, PhD,*
Fabıola Dach, PhD,†
sar Ferna
Ce ndez-de-las-Pen~ as, PhD,‡
bora Bevilaqua-Grossi, PhD*
and De
*Department of Biomechanics, Medicine and Locomo-
tor Apparatus Rehabilitation; †Department of Neuro-
sciences and Behavioral Sciences, Faculty of
~o Preto, University of Sa
Medicine of Ribeira ~o Paulo,
~o Preto-SP, Brazil; ‡Department of Physical
Ribeira
Therapy, Occupational Therapy, Physical Medicine
and Rehabilitation, Universidad Rey Juan Carlos,
Alcorcon, Spain
Reprint requests to: Lidiane Lima Florencio, MD,
Avenida Bandeirantes, 3900 – Monte Alegre CEP
14049-900, Ribeira ~o Preto/SP A/C Fisioterapia.
Tel.: 1551198579-1787; Fax: 155 16 3315-4413;
E-mail: lidianelimaflorencio@gmail.com.
Conflict of interest: The authors state that there is no
conflict of interest.
Funding sources: This study received financial sup-
~o Paulo Research Foundation (FAPESP).
port from Sa
Abstract
Objective. To investigate the differences in pres-
sure sensitivity in the cervical musculature includ-
ing the upper trapezius, sternocleidomastoid,
suboccipital, levator scapulae, and anterior scalene
muscles between women with migraine and healthy
controls.
Design. Cross-sectional study.
Subjects. Thirty women with migraine and 30
healthy women participated.
Methods. Pressure pain thresholds (PPT) were
bilaterally assessed over upper trapezius, sterno-
cleidomastoid, suboccipital, levator scapulae, and
anterior scalene muscles in a blinded design. Mean
values of both sides were pooled for statistical anal-
ysis. Comparison between groups was performed
by unpaired Student t-test and correlation with
headache features with Spearman’s correlation test.
Results. Migraine patients exhibited lower PPT in
all muscles compared with controls: upper trape-
zius (P 5 0.046); suboccipital (P < 0.001); sternoclei-
domastoid (P < 0.001); anterior scalene (P < 0.001),
and levator scapulae (P < 0001). No associations
were observed between the frequency and the
intensity of migraine or years with the disease and
PPT.
Conclusion. This study showed generalized pres-
sure pain hypersensitivity in the cervical muscula-
ture in women with migraine. Our findings provide
support for the physical therapy treatment and eval-
uation of musculoskeletal cervical spine disorders
in individuals with migraine and reinforce that all
cervical muscles should be evaluated.
Key Words. Pressure Pain Threshold; Cervical
Spine; Muscles; Migraine
Introduction
Migraine is a chronic pain disease with recurrent epi-
sodes affecting between 5% and 12% of the general
population [1–3]. Accordingly to the diagnostic criteria
suggested by the International Headache Society,
migraine headache attacks are mainly characterized by
headaches lasting from 4 to 72 hours, throbbing and
pulsating quality, of moderate to severe intensity, which
can be exacerbated by routine physical activity and is
associated with nausea, vomiting, photophobia, and/or
phonophobia [4]. However, other clinical features have
been also highlighted as being important in predicting
the prognosis of migraine pain, such as the presence of
neck pain [5].
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Florencio et al.
The prevalence of neck pain in patients with migraine is
almost 76% [6], and it may appear in the premonitory
phase or accompany the headache phase [7]. Neck
pain is more prevalent than nausea during migraine
attacks [8] and is an important predictor of disability in
migraine patients [5–7], capable of delaying the thera-
peutic effect of abortive drug treatment [9].
Several musculoskeletal impairments of the cervical
spine are usually seen in patients with migraine includ-
ing restricted cervical range of motion, presence of
myofascial trigger points, increased muscle hypersensi-
tivity, forward head posture, and reduced pressure
pain thresholds (PPT); [10–12]. The relationship
between neck pain and migraine can be explained by
the trigeminocervical nucleus caudalis, which is the
anatomical region where the nociceptive afferences
from the upper cervical and trigeminal nerves con-
verge. Therefore, cervical spine stimulation can cause
pain in any area innervated of the trigeminal nerve [13].
The cervical spine can be considered as a hidden irri-
tative thorn where a continuous bombardment of noci-
ceptive stimuli may lead to the hyperexcitability of the
central nervous system seen in patients with migraine
[14,15].
Pressure pain hypersensitivity, expressed as decreased
PPT, is generally regarded as a common clinical mani-
festation of sensitization of nociceptive pain pathways.
Previous studies investigating PPT on migraine patients
reported conflicting results as some studies have
observed lower values in patients when compared with
controls [16–19]; whereas others reported no differen-
ces in PPT between migraine, tension-type headache,
and healthy subjects [20,21]. These previous studies
only investigated pressure pain sensitivity in the tempo-
ralis or upper trapezius muscle, but mechanical sensitiv-
ity of other cervical muscles in individuals with migraine
has not been determined yet. To determine the pres-
ence of pressure hypersensitivity in other cervical
muscles can contribute to deeper understanding of the
clinical features in patients with migraine and to more
integrative clinical evaluation of this population.
The aim of this study was to investigate differences in
pressure pain sensitivity in the neck musculature includ-
ing the upper trapezius, sternocleidomastoid, suboccipi-
tal, levator scapulae, and anterior scalene muscles
between migraine patients and controls subjects. Our
hypothesis was that migraineurs exhibit lower PPT com-
pared with individuals without migraine in all the
muscles evaluated.
Methods
Participants
Patients with headache from a university-based head-
ache center were screened for eligibility criteria. Migraine
patients were diagnosed following the International
Headache Society criteria by an experienced neurologist
1630
[4]. In all participants, headache features including time
of disease, frequency and intensity of migraine attacks,
family history, and medications were assessed from the
clinical history. Patients were excluded if presented
other primary headaches; medication overuse head-
ache; pregnancy; systemic degenerative diseases such
as rheumatoid arthritis, lupus erythematous, or other
medical diseases affecting sensitivity, for example, such
fibromyalgia or previous neck trauma (whiplash). A care-
ful examination of each participant was conducted to
determine inclusion and exclusion criteria. Control group
without migraine history were selected at the same hos-
pital and matched by age to migraine group. The study
was approved by the local Ethics Committee (process
2013/08836-0). All participants in the study signed the
informed consent form.
Pressure Pain Thresholds
PPT was assessed using a digital manual dynamome-
ter (DDK-10 Kratos) adapted for algometry evaluation.
The device’s calibration ranges from 0 to 29 kg with
an accuracy of 0.001 kg. A 1-cm2 rubber disk was
adapted to the device’s metal point to avoid any harm.
PPT was bilaterally assessed at the following five
muscles in a random sequence for two consecutive
series: (X1) sternocleidomastoid (fibers below the mas-
toid process); (X2) levator scapulae (central point
between the proximal portion of the sternocleidomas-
toid and upper trapezius insertion); (X3) suboccipital
(below the occipital bone, lateral to upper trapezius
insertion); (X4) upper trapezius (midpoint between the
C7 spinous process and the acromion); and (X5) ante-
rior scalene (middle portion between the transverse
processes of the cervical vertebrae and the first rib)
(Figure 1).
The examiner was blinded to the subject’s condition.
The examiner was previously trained to apply a constant
pressure of about 1 kg/cm2/s with optimal positioning of
the device perpendicular to the evaluated anatomical
surfaces. A digital metronome with a frequency of 1 Hz
was used in all evaluations for providing an audio feed-
back and standardization of the pressure application
speed to the examiner. The order of point assessment
was randomized between participants.
Participants were informed that the evaluation was to
determine the pain threshold and not pain tolerance;
therefore, they were asked for signaling as soon as they
first felt pain. All participants were firstly trained with a
first assessment on the thenar region of the right hand.
The evaluation was held when all migraine patients were
headache-free, and when at least 1 week had elapsed
since the last migraine attack to avoid migraine-related
allodynia. All patients were being taken prophylactic
drugs, but none of them was taking any migraine abor-
tive drug at the time of the study. No other medication
inferring in pressure sensitivity, such as muscle relaxants
or antipsychotics, was permitted.

Figure 1 Anatomical sites of PPT assessment: (X1) Sternocleidomastoid; (X2) Levator Scapulae; (X3)
Suboccipital; (X4) Upper Trapezius; and (X5) Anterior Scalene.
Sample Size Determination
The sample size determination was performed with an
appropriate software (Taman ~o de la Muestra, 1.1VC,
Spain). The calculations were based on detecting, at
least, significant clinically differences of 20% on PPT
between groups [22] with an alpha level of 0.05, a
power of 80%, and an estimated interindividual coeffi-
cient of variation for PPT measures of 20%. This gener-
ated a sample size of at least 16 participants per group.
Statistical Analysis
Data were analyzed with Statistical Package for Social
Scientist package version 18.0 (SPPS Inc, ChicagoV C ).
Means, standard deviations or 95% confidence intervals
were calculated. As no side-to-side differences were
observed, mean of both sides were used in the main
analysis for between-groups comparisons. The unpaired
Student t-test was used to investigate differences in
PPT between patients with migraine and healthy con-
trols. The Spearman’s rho (rs) test was used to analyze
the association between the intensity and frequency of
migraine and history (years) with the disease with PPT
over each muscle within the migraine group. For linear
associations, values <0.3 represent weak correlation;
Table 1 Clinical and demographic features of patients with migraine and healthy controls
Age BMI
(years) (kg/m2)
Migraine 37 6 12 (33, 42) 26 6 7 (24, 29)
(n 5 30)
Healthy 32 6 10 (28, 35) 26 6 6 (24, 28)
controls
(n 5 30)
Data are means 6 standard deviations (95% confidence intervals).
Neck Muscles PPT in Migraine
from 0.3 to 0.7 moderate correlation; and >0.7 strong
correlation [23]. The analysis was conducted at 95%
confidence level. A P value less than 0.05 was consid-
ered statistically significant.
Results
From January 2014 to June 2014, 418 potentially eligi-
ble subjects were screened. Three hundred and fifty-
three (n 5 353, 87%) were excluded due to the following
reasons: another type of primary headache (n 5 180),
age (n 5 73), associated medical diseases that may
interfere the sensibility such as fibromyalgia (n 5 82),
refute to participate (n 5 18) and male gender (n 5 5).
Were analyzed 30 women, aged from 18 to 55 years
(mean: 37 years), with migraine and 30 healthy women,
aged from 18 to 50 years (mean: 32 years). All partici-
pants were taking amitriptyline as a prophylactic medi-
cation on their regular basis. No significant differences
were found in age and body mass index between both
groups (Table 1).
The results revealed that patients with migraine exhib-
ited lower PPT in all muscles compared with controls:
upper trapezius (t 5 2.014; P 5 0.046); suboccipital
(t 5 6.489; P < 0.001); sternocleidomastoid (t 5 7.960;
History of
disease Frequency Intensity
(years) (days/month) (VAS)
16 6 14 (11, 21) 10 6 9 (7.0, 13.4) 8 6 1.6 (7.6, 8.8)
- - -
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Florencio et al.

Table 2 Differences in pressure pain thresholds (PPT) of the cervical musculature between patients with
migraine and healthy control

Migraine Healthy Between-Group

Patients (n 5 30)* Controls (n 5 30)* Differences†

Upper Trapezius‡ 2.5 6 0.1 2.8 6 0.2 0.3 (0.1, 0.6)

Suboccipital‡ 1.6 6 0.1 2.4 6 0.1 0.8 (0.5, 1.0)
Sternocleidomastoid‡ 1.6 6 0.1 2.5 6 0.1 0.9 (0.7, 1.1)
Scalene‡ 1.4 6 0.1 2.2 6 0.1 0.8 (0.6, 1.0)
Levator Scapulae‡ 1.7 6 0.1 3.0 6 0.1 1.3 (1.0, 1.6)

* Data are means 6 standard deviations.

†
Data are means (95% confidence intervals).
‡
Significant differences between patients and controls (Student t-test, P < 0.01).

P < 0.001); anterior scalene (t 5 6.985; P < 0.001); and including the levator scapulae, anterior scalene and sub-
levator scapulae (t 5 8.673; P < 0.001; Table 2). occipital muscles in episodic migraine.

No significant associations were observed between the
frequency or intensity of the migraine or the years with
the disease and PPT in the cervical muscles (Table 3).
Discussion
This study showed generalized pressure pain hypersen-
sitivity in the cervical musculature as expressed by
decreased PPT levels over the upper trapezius, subocci-
pital, levator scapulae, sternocleidomastoid, and anterior
scalene muscles in women with migraine compared
with controls. No significant associations were found
between PPT and the headache clinical variables.
The presence of mechanical pain hypersensitivity is not
new in patients with migraine as previous studies have
reported lower PPT in this population [16–19]; neverthe-
less, these studies investigated only the temporalis or
upper trapezius muscles. The best our knowledge, this
study is the first one that demonstrated the generalized
pressure pain hypersensitivity over cervical musculature
The neurophysiological and morphological evidence of
convergence from cervical sensory and muscle afferent
inputs onto trigeminal subnucleus caudalis is considered
an explanation for the phenomenon of cervical to tri-
geminal and trigeminal to cervical pressure pain hyper-
sensitivity. The clinical implication of this coexistence is
the beginning of a vicious cycle where the nociceptive
cervical afferents induces a constant bombardment on
trigeminocervical nucleus caudalis, causing suprathres-
hold stimuli and triggering migraine attacks. Conse-
quently, leading to generalize reduced mechanical pain
thresholds of cervical muscles. Additionally, the pres-
ence of generalized mechanical sensitivity over the cer-
vical musculature is generally explained by central
sensitization mechanisms seen in patients with migraine
that has already been described by several authors
[14,15]. Nevertheless, we cannot confirm the presence
of central sensitization as we did not assess PPT over
pain-free distant points, for example, tibialis anterior
muscle. Therefore, current results support that individu-
als with migraine exhibit sensitization mechanisms, at
least, of the trigeminocervical nucleus caudalis, as PPT

Table 3 Spearman rho (rs) correlation coefficients between clinical variables and pressure pain
thresholds within the migraine group

Migraine Frequency Years With Migraine Diagnosis

Migraine Intensity
95% Confidence 95% Confidence 95% Confidence
rs interval P rs interval P rs interval P

Upper Trapezius 20.20 20.43, 0.05 0.12 20.01 20.26, 0.24 0.95 0.32 20.07, 0.53 0.10
Suboccipital 20.07 20.32, 0.19 0.57 20.14 20.37, 0.12 0.30 0.20 20.05, 0.43 0.12
Sternocleidomastoid 20.20 20.43, 0.06 0.13 20.06 20.32, 0.19 0.62 0.17 20.09, 0.41 0.18
Scalene 20.16 20.40, 0.09 0.21 20.03 20.28, 0.22 0.80 20.07 20.32, 0.19 0.59
Levator Scapulae 20.23 20.46, 0.02 0.07 20.01 20.26, 0.24 0.94 20.19 20.40, 0.13 0.23

1632

were lower in cervical muscles innervated by different
cervical segments. Alternatively, it is also possible that
our results are a manifestation of peripheral sensitization
mechanisms on the cervical musculature as women
with migraine exhibit myofascial trigger points in these
muscles [12]. We do not currently know if any of the
points over we assessed PPTs exhibited trigger points
explaining the pressure pain hyperalgesia.
The evaluation and specific therapeutic approach for
patients with migraine focused on the cervical spine
generally emphasize essential management of the upper
trapezius and sternocleidomastoid muscles [24].
Although these muscles are hypersensitive, we also
found that other neck muscles, including the levator
scapulae, suboccipital, and anterior scalene may be
also relevant for individuals with episodic migraine.
These findings provide support for the physical therapy
treatment and evaluation of musculoskeletal cervical
spine disorders in individuals with migraine and reinforce
that all cervical muscles should be evaluated. Current
results contribute to a better understanding of cervical
disorders in patients with migraine and justify cervical
disability [5] and the need to consider these aspects for
proper management of these patients.
Finally, we should recognize some limitations of our
study. First, we cannot establish cause-and-effect rela-
tionship between migraine and generalized pressure
hypersensitivity, because the design was not longitudi-
nal. Second, we included only women with migraine.
Previous studies have shown that women exhibit greater
susceptibility to the development of mechanical hyper-
sensitivity than men [25]. Therefore, these results may
not be applicable to male subjects with migraine. Third,
we did not control the potential effect of prophylactic
treatment. All women were taking their regular basis
doses of amitriptyline. We do not know if prophylactic
treatment could influence pressure pain sensitivity; how-
ever, a study observed that amitriptyline did not affect
PPT in subjects with tension-type headache [26].
Fourth, we did not assess the presence of psychological
disorders, including anxiety and depression, which
could potentially influence the results. Finally, our
patients were recruited from a tertiary outpatient clinic
explaining the high number of subjects screened but
excluded from the study; therefore, it is possible that
our sample represent a particular and specific subgroup
of the population with migraine. Future epidemiological
studies are now needed to finally determine the pres-
ence of generalized or widespread pressure pain hyper-
algesia in patients with migraine.
Conclusion
This study showed generalized pressure pain hypersen-
sitivity in the cervical muscles as expressed by
decreased PPT levels over the upper trapezius, subocci-
pital, levator scapulae, sternocleidomastoid, and anterior
scalene muscles in women with migraine. No significant
Neck Muscles PPT in Migraine
associations were found between PPT and the head-
ache clinical variables.
Acknowledgments
The authors want to acknowledge Professor Jose  Geraldo
Speciali for the trial support and Sa ~o Paulo Research
Foundation (FAPESP) for the financial support.
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