Local Inflammation as a Mediator of Migraine

and Tension-Type Headache

Mark H. Friedman, DDS

Objective.—To demonstrate the relationship of migraine and tension-type headache to a localized maxillary
gingival inflammation.
Background.—Intraoral tenderness has been observed consistently in the most common types of primary
headache disorders. The laterality and degree of tenderness is related to laterality and severity of reported symptoms,
both during headache and in the interictal state.
Methods.—Bilateral posterior maxillary palpation and local temperature recordings were performed during
unilateral migraine and tension-type headache. Local anti-inflammatory techniques, ie, local chilling and a topical
anti-inflammatory gel, were used in these tender areas in episodic migraine and tension-type headache patients.
Results.—Ipsilateral intraoral tenderness and increased local temperature were consistently observed during
unilateral migraine and tension-type headache, suggesting local inflammation. Intraoral chilling and topical appli-
cation of a nonsteroidal anti-inflammatory drug were highly effective for the treatment of migraine and tension-type
headache, both in the acute phase and for headache prevention.
Conclusion.—These results suggest that a local intraoral inflammation may be associated with the pathogenesis
of these common headaches.
Key words: intraoral tenderness, inflammation, migraine, tension-type headache, topical nonsteroidal anti-
inflammatory drugs
Abbreviations: TTH tension-type headache, MAT maxillary alveolar tenderness, TMJ temporomandibular joint
disorders, ICH intraoral chilling procedure
(Headache 2004;44:767-771)

Headache may be the most common complaint
of civilized man, with migraine and tension-type
headache (TTH) comprising the bulk of this disorder.1
Migraine has been generally attributed to a neurogenic
dural inflammation with plasma extravasation caused
by neuropeptide release.2,3 Considerable research has
led to many specific antimigraine drugs. TTH re-
search, conversely, has been minimal, and knowledge
about key pathophysiological factors is limited.4,5 In
From the Clinical Associate Professor of Medicine, New York
Medical College; Clinical Associate, Professor of Anatomy &
Cell Biology, New York Medical College, Valhalla, NY; Clinical
Associate Professor of Dentistry, Westchester Medical Center,
Valhalla, NY.
Address all correspondence to Mark H. Friedman, DDS,
Westchester Head & Neck Pain Center, 2 Overhill Rd., Ste. 260,
Scarsdale, NY 10583.
Accepted for publication April 12, 2004.
the Handbook of Headache Management, Saper and
Silberstein state “because of the significant uncer-
tainty regarding most aspects of this disorder and the
strong differences of opinion that prevail, the authors
of this book have decided against a detailed review of
this entity.”6
In preliminary data analysis performed in the au-
thor’s office, intraoral tenderness in the maxillary mo-
lar periapical area (Figure 1) was identified in 1026
of 1100 (93.2%) mostly asymptomatic migraine and
TTH patients, with laterality and degree of tenderness
closely related to laterality and severity of reported
symptoms.7 When examined bilaterally during unilat-
eral migraine or TTH, this maxillary alveolar tender-
ness (MAT) demonstrated significant ipsilateral ten-
derness and increased local temperature.8 The MAT is
also present in cervical muscle spasm9 and facial pain
patients, with the latter also exhibiting increased local

767
768
Fig 1.—The apical area of the maxillary third molar (arrow) is
the center of the zone of tenderness.
temperature.10 Usually absent in normal individuals,
the MAT occurs even if the area is edentulous. It was
only occasionally found in two control groups of pain-
free individuals and those with temporomandibular
disorders (TMJ).10 This MAT is frequently described
as lateral pterygoid muscle spasm, although this mus-
cle is inaccessible to palpation.11,12 The research has
noted the consistent occurrence of tenderness and in-
creased local temperature—signs of inflammation—in
migraine and TTH. This article explores the possibility
that a local inflammation may be related to migraine
and TTH etiology.
METHODS
Selection of Patients.—Patients were recruited
randomly over an 8-year period from the author’s pri-
vate practice, the Westchester Medical Center Depart-
ments of Emergency Medicine and Dentistry, the New
York Medical College Departments of Medicine and
Neurology, and Our Lady of Mercy and St. Agnes
Hospitals. A total of 1220 men and women from 18
to 70 years old, diagnosed according to International
Headache Society (IHS) criteria13 for episodic mi-
graine or TTH, were examined intraorally. Of these, 40
were evaluated for local tenderness and temperature,
60 were treated in two chilling studies, and 20 were
treated in the topical gel study.
Treatment for the chilling studies was approved
by the New York Medical College and Westchester
Medical Center Institutional Review Boards (IRBs),
and the procedure was classified as a nonsignificant
risk. It involved hollow metal tubes chilled by circu-
September 2004
Fig 2.—Intraoral tube placement. Disposable plastic sheath is
eliminated for photographic clarity. Arrows indicate the direc-
tion of ice-water flow.
lating ice water held over the MAT bilaterally by the
patient for 40 minutes (Figure 2). Written informed
consent was obtained. The Allendale Investigational
Review Board approved the topical gel study with oral
informed consent.
Palpation and Temperature Recordings.—The
posterior maxillary area (Figure 1) was palpated bi-
laterally in 1100 patients with a history of episodic
migraine and/or TTH. Laterality and degree of ten-
derness and local temperatures were recorded bilat-
erally with a digital long-stem laboratory thermome-
ter (Edmund Scientific, Barrington, NJ). Patients’
headache history, i.e., laterality, severity, frequency, as
well as current symptoms were also recorded. The ma-
jority of patients were asymptomatic at the time of the
examination. The study was performed in the author’s
office and at the Westchester Medical Center Dental
(TMJ) Clinic.7
Palpation and Temperature Recordings During
Unilateral Migraine and TTH.—On 40 subjects ex-
periencing unilateral episodic migraine or TTH at
the time of the examination, the posterior molar
areas were palpated bilaterally, and their tempera-
tures recorded. This study was performed in the de-
partments of medicine, neurology, and emergency
medicine at a tertiary care academic medical center,
a community hospital, and the author’s office.8
Emergency Department Migraine and TTH
Study.—Twenty-five patients, including pregnant
Headache
women, presenting to the Westchester Medical Cen-
ter Emergency Department with acute migraine or
TTH (average duration more than 30 hours), were
treated solely by local treatment to the MAT area.
Eight emergency medicine physicians used an experi-
mental device designed to circulate ice water through
hollow metal tubes (Figure 2). The tubes were held
over the posterior maxillary gingiva by the patients for
40 minutes.14 This device and intraoral chilling pro-
cedure (ICH) have been approved by the U.S. Food
and Drug Administration for the reduction of muscle
spasm, and more recently, for migraine treatment.7
In initial intraoral chilling experimentation, uni-
lateral treatment occasionally caused symptoms and
MAT to shift to the contralateral side. Therefore, re-
gardless of laterality of symptoms, bilateral chilling is
used. Ice-cream headache,13 occurring from cold stim-
ulus on the palate, did not occur during the studies
(below), but was noted in prior experimentation, when
probe placement was less efficient.16
Department of Medicine Controlled Migraine
Study.—Thirty-five symptomatic episodic migraine
patients were treated in the outpatient department
of the New York Medical College Department of
Medicine and a faculty practice at St. Agnes Hospital
during severe migraine (average duration 17.4 hours).
In a randomized fashion, the patients were treated by
40 minutes of ICH, as in the above experiment, 50 mg
of oral sumatriptan, or 40 minutes of tongue chilling,
using the same device.15
Topical NSAID Gel Study.—Twenty episodic mi-
graine, TTH, and post-traumatic headache patients
were enrolled in an open-label headache prevention
study. Fifteen of the patients were referred by the
co-authors of previous studies. Patients kept a daily
headache diary for 60 days, recording headache type,
frequency, severity (1 to 10 scale), duration (hours),
headache medications and analgesics taken, and side
effects. During the second 30 days, medication was ap-
plied. Ketoprofen was compounded with organogel to
create a gel, serving as the vehicle to deliver the drug
to the tissue. Patients placed a disposable cheek shield
between the molar teeth and the cheek for 30 minutes,
and applied the gel to the tissue bilaterally, using a cot-
ton applicator (Figure 3). This procedure was followed
once daily. If symptoms were exclusively unilateral,
769
Fig 3.—(A) Cotton tip applicator with medication contacting the
apical area of the maxillary third molar. (B) Disposable cheek
shield.
the medication was applied to the symptomatic side
only.16
RESULTS
Palpation and Temperature Examination.—MAT
was palpated in 1026 out of 1100 (93.2%) mostly
asymptomatic migraine and TTH patients, with lat-
erality and degree of tenderness closely related to
laterality and severity of symptoms. A consistent re-
lationship between symptom laterality and increased
local temperature was observed only in symptomatic
patients.
Palpation and Temperature Recordings During
Unilateral Headache.—In 40 patients experiencing
unilateral migraine or TTH, the ipsilateral MAT tem-
perature was consistently higher (37 of 40) and the area
more tender (39 of 40). Significant correlations were
found between laterality and severity of symptoms to
laterality and degree of tenderness, and between tem-
perature and tenderness differentials. Kappa statistics
demonstrated good agreement between laterality of
temperature differential and tenderness, laterality of
tenderness and symptoms, and laterality of tempera-
ture differential and symptoms.8
Emergency Department Acute Headache Chill-
ing Study.—Twenty of 25 severe headache patients, in-
cluding pregnant women, were relieved of symptoms
within 1 hour, using only bilateral ICH. With symp-
toms rated from 0 to 10, the mean migraine score went
from 7.74 to 2.7 and the mean TTH score went from
770
7.8 to 1.2. Next-day follow-up scores for the migraine
and TTH patients were 1.6 to 0.8, respectively. No side
effects were reported.14
Acute Migraine Controlled Chilling Study.—
Significant mean headache relief was obtained by ICH
and sumatriptan at 1, 2, 4, and 24 hours after the initia-
tion of treatment, with poor relief obtained by placebo
(0 to 10 scale). ICH was more effective for headache
relief than sumatriptan at all four time intervals. Sig-
nificant nausea relief was obtained by ICH and suma-
triptan at the same post-treatment time intervals. At
24 hours, some headache and nausea recurrence was
noted with sumatriptan, but not with ICH.
Results at pre, post, 2, 4, and 24 hours later: for
sumatriptan 7.3, 4.6, 3.54, 2.75, and 2.92; for intraoral
chilling 7.33, 3.5, 2.33, 2.04, and 1.1; for tongue chilling
7.2, 6.0, 5.6, 5.8, and 4.36.15
Topical Ketoprofen Headache Prevention
Study.—Headache burden, which equals total
monthly headache hours × average severity (0 to 10
scale) decreased from 454.8 (30-day baseline) to 86.5
P < .001 during the 30-day treatment phase. Analgesic
and headache medication intake were significantly
reduced from baseline during the treatment phase,
with minimal side effects.16
COMMENTS
Intraoral tenderness, closely related to migraine
and TTH, increases during a headache, and is absent
in pain-free individuals. This headache marker is usu-
ally present, but less severe, in chronic daily headache.
The MAT appears to be absent in lesional headaches
and intracranial bleeds, based on limited emergency
department patient observations.
Migraine theory describes plasma extravasation
(edema) secondary to inflammation.2,3 Our local treat-
ment basically consists of reduction of inflammation
to reduce edema, ie, local vasoconstriction. Intra-
oral chilling appears to affect the small, unmyelinated
C fibers responsible for deep muscular pain, rather
than the larger, myelinated A-delta fibers producing
sharper, more sudden pain. In seven nonstudy patients
who responded positively to ICH, prior therapy did not
ameliorate pain elicited by the application of electric
current to the maxillary incisor labial surfaces or dry
needling masseter muscle trigger points. This result is
September 2004
consistent with the fact that dural inflammation can
be induced in experimental animals, but not in those
in whom C fibers were previously destroyed.17
Local tenderness and increased temperature sug-
gest inflammation.18 Application of two local anti-
inflammatory techniques produced profound clinical
results,14-16 both in initial patient findings (reviewed
by the Westchester Medical Center and New York
Medical College IRBs) and in our study patients. The
results appear equally related to both migraine and
TTH,8,14,16 which occur together more frequently than
would be expected by chance. Most migraineurs (62%)
also have TTH, and 25% of TTH patients also have mi-
graine.19 Our findings, related to both conditions, sug-
gest a similar etiology. In clinical practice, patients are
usually treated with both techniques; ICH is used ini-
tially, and soon afterward, the topical gel is prescribed
for home use.20
To identify the MAT area, the maxillary second
and third molar periapical areas are palpated bilat-
erally, even if the area is edentulous. The examiner’s
index finger is pressed backward and upward as far as
possible, along the vestibule between the cheek and
the alveolar mucosa, with the mouth partially opened
(mid-range). If necessary for clearance, patients may
be instructed to move the mandible laterally to the
side being examined. The palpation proceeds from
the posterior molar area as far forward as the first
premolar. MAT does not usually extend this far an-
teriorly, but tenderness can be better appreciated if
contrasted with a normal area.8 Since laterality and
degree of tenderness are so closely related to reported
migraine and TTH symptoms, palpation can easily be
performed as an initial evaluation of this local in-
flammation headache theory, before dismissing it as
“voodoo.”21 Regarding the placebo effect, a significant
percentage of placebo-treated patients suffer relapse
24 hours later,22 unlike our treated patients.
In conclusion, a localized area demonstrating
symptom-related tenderness, increased temperature,
and profound symptomatic response to two local anti-
inflammatory techniques suggests that a local inflam-
mation may mediate these common headaches. This
would explain why “for moderate to severe headaches,
aspirin works better than acetominophen.”23 A large-
scale study will aid in further determining the relation
Headache
of migraine and TTH to this local pathology, and more
accurately gauge the effectiveness of local treatments.
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