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ABSTRACT
RESUMO
Descritores: Atividade Física, Exercício Físico, Migrânea, Fatores
Desencadeantes, Estresse.
ORIGINAL ARTICLE
Aerobic exercise training for migraine prevention: A
trigger-based analysis
Treinamento físico aeróbico na prevenção da migrânea: Uma
análise de fatores desencadeantes
Arão Belitardo Oliveira
1,2
*
Diego Belandrino Swerts
3
Mario Fernando Prieto Peres
1,3
1
Universidade de São Paulo, Instituto de
Psiquiatria, Hospital das Clínicas da Faculdade
de Medicina, 785, Rua Dr. Ovídio Pires de
Campos, CEP: 05403-903, São Paulo - SP,
Brazil.
2
Universidade Federal de São Paulo,
Departamento de Neurologia e Neurocirurgia,
669, Pedro de Toledo, CEP 04039-032 São
Paulo, Brazil.
3
Hospital Israelita Albert Einstein, Brain
Institute, 627/701, Avenida Albert Einstein, CEP
05652-900, São Paulo, Brazil.
*Correspondence
Arão Belitardo Oliveira
E-mail: araoliva@gmail.com; aboliveira@
unifesp.br
Received: February 15, 2019.
Accepted: February 25, 2019.
Background: Although aerobic exercise has been recommended for migraine
management, no study has yet explored the effects of regular aerobic exercise
on migraine triggers prole. Objective: To evaluate the effects of a 12-week
aerobic exercise intervention on migraine triggers prole. Methods: We
conducted a secondary, post hoc analysis of a randomized, controlled clinical
trial. Triggers were recorded in a paper-based headache diary with a formal list
including 8 common migraine triggers. Results: Twenty-ve patients concluded
the protocol and were analysed (exercise: n = 12; waitlist: n = 13). In the whole
cohort, the most common triggers were stress/irritability (60 %), sleep
deprivation (60 %), fasting (28 %), and foods (28 %). Most patients (52 %) had ≥
3 triggers. The exercise group showed a higher baseline proportion of patients
with ≥ 3 triggers (69 %) compared to waitlist group (25 %) (p = 0.041). After
intervention period, there was no difference in the proportion of patients with ≥
3 triggers between waitlist (16.6 %) and exercise (30 %) groups (p = 0.502). The
exercise group showed greater numeric reductions (from group’s sum) than
waitlist group for triggers stress/irritability (-14 vs -9), fatigue (-12 vs -6), and
menstruation (-9 vs -5). This seemed to reect the reduced number of attacks
in the exercise group [mean (CI95 %): -2.5 (-3.7, -1), p = 0.002] vs waitlist [0.9
(2.4, -0.8), p = 0.341]. Conclusion: Tracking migraine triggers during exercise
interventions may help to unravel specic clinical effects of regular exercise.
Trial registration: #NCT01972607.
Keywords: Physical Activity, Exercise, Stress, Treatment, Triggers.
Embora o exercício aeróbico seja recomendado no tratamento da migrânea,
nenhum estudo seu efeito no padrão de fatores desencadeantes das crises,
os chamados “gatilhos”. O objetivo desse estudo foi avaliar se um programa
de exercícios aeróbicos de 12 semanas afeta o perl de gatilhos reportados
pelos pacientes. Foi realizada uma análise secundária post hoc de um estudo
controlado e randomizado. Os gatilhos foram registrados em diário da dor
impresso contendo uma lista de 8 gatilhos frequentemente reportados na
literatura. Vinte e cinco participantes concluíram o protocolo e foram analizados.
Na amostra total, os gatilhos mais comuns foram estresse/irritabilidade (60
%), privação do sono (60 %), jejum (28 %) e alimentos (28 %). A maioria dos
pacientes (52 %) reportaram ≥ 3 gatilhos. O grupo exercício mostrou maior
proporção de pacientes com ≥ 3 gatilhos (69 %) no período pré intervenção em
comparação com o grupo controle (25 %) (p = 0.041). Após intervenção, essa
diferença não foi observada (exercício = 30 % vs controle = 16.6, p = 502). O
grupo exercício mostrou maior redução numérica (dados de soma dos gatilhos
por grupo) em comparação com o grupo controle para os gatilhos estresse/
irritabilidade (-14 vs -9), fadiga (-12 vs -6) e menstruação (-9 vs -5). Esse efeito
reetiu redução no número dos ataques no grupo exercício [média (IC 95 %):
-2.5 (-3.7, -1), p = 0.002] vs grupo controle [0.9 (2.4, -0.8), p = 0.341]. O registro
no padrão de gatilhos durante intervenções com exercícios pode auxiliar no
rastreio de efeitos clínicos especícos ainda não estudados. Registro do estudo
clínico: NCT01972607.
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INTRODUCTION
Growing body of evidence has strengthened the
therapeutic benets of regular physical activity for the
management of migraine
1
. In particular, aerobic exercise
performed at moderate intensity and practiced 3 times
per week is accounted for reducing around 30-40 % the
number of migraine attacks/days with migraine2–4),
with therapeutic effects comparable to preventive
medication
5,6
. Other health outcomes such as perceived
stress, mood, and well-being may also improve by
adopting aerobic exercise as an adjunct treatment for
migraine
2,7,8
. However, there are still other unexplored
effects of aerobic exercise on clinical aspects of migraine,
such as the triggers prole of patients.
Many patients perceive a myriad of internal or
external stimuli as precipitants of migraine attacks, the
so-called triggers
9–13
. A recent meta-analysis showed
that nearly 90% of headache patients report at least one
consistent trigger
9
. The most common triggers reported
by patients include stress, sleep deprivation, fasting,
certain foods, menstruation, to name a few
9
. While
physical exercise is also considered a trigger by around
20-40 % of patients
14,15
, many evidences from clinical and
epidemiological studies strengthen the recommendation
of regular aerobic exercise, and the current understanding
is that the protective effect outweighs possible harmful
triggered during exercise
1,16
. In fact, exercise imposes a
challenge to homeostasis at molecular and physiological
levels in several neurobehavioral and physiological
processes, it could interact with mechanisms thought
to be involved in migraine triggers, such as sleep, stress
response, hydration, hypoglycaemia, and so forth to
either worse/precipitate the attacks or prevent them
1,17
.
In this sense, exploring the patient´s trigger pattern
while engaging in an exercise training program may
have clinical and behavioural implications, and even
affect exercise prescription recommendation for this
population. Therefore, it is necessary to understand
better the relationship between aerobic exercise and
migraine under the perspective of triggers factors. To
our knowledge, no study has yet evaluated the response
of regular aerobic exercise on the triggers’ prole of
migraine patients. Thus, the scope of this study was to
evaluate the trigger prole of a migraine patient cohort
following a 12-week aerobic exercise program. Because
there is inter-person variability for triggers, we did not
set any a priori hypothesis. We rather conducted an
exploratory data analysis, then provided contextual
interpretation based on current literature.
METHODS
Study Design
This study consists of a secondary, post hoc, per-
protocol analysis of an open-label, randomized controlled
clinical trial aiming to assess clinical outcomes in migraine
patients following a 12-week aerobic exercise program
2
.
We retrospectively analysed the triggers recorded in the
headache diary of patients.
The study protocol was approved by the Research
Ethics Committee of the Sao Paulo Federal University,
and have therefore been performed in accordance with
the ethical standards laid down in the 1964 Declaration of
Helsinki and its later amendments. All participants gave
their informed consent prior to their inclusion in the study.
The trial has been registered in the National Institute of
Health (www.ClinicalTrials.gov) under #NCT01972607.
The study complies with the CONSORT’s Statement on
data reporting for non-pharmacological trials
18
.
Participants
Participants were recruited and screened in the
Neurology Department of the Sao Paulo Federal
University. The inclusion criteria were: subjects of both
sexes, between 18 and 65 years, physically inactive
the previous 12 months (dened as ≤ 1 day/week of
leisure-time physical activity). Exclusion criteria were:
patients taking any prescribed medication or dietary
supplements; practicing mind-body activities (e.g., yoga,
tai chi, etc.); pregnancy; clinical history of cardiovascular,
pulmonary, metabolic, rheumatic, musculoskeletal,
psychiatric, or other neurological disease. All participants
had a neurological and cardiological examination before
inclusion in study.
Migraine Triggers Assessment
Clinical data were retrieved from paper-based
headache diary. Besides the data on migraine frequency,
the diary had a formal list including eight common
migraine triggers: “stress/irritability”, “sleep deprivation”,
“oversleep”, “fasting”, “foods”, “odours”, “photic stimuli”,
“alcohol”, and “other” for non-listed factors. If there were
no identiable triggers, patients were instructed to let
the option for description blank.
Statistical Analyses
Descriptive statistics and comparison between
groups for participants’ characteristics were calculated
by independent t-test (normal distribution assumed).
Within-group differences for migraine frequency
(continuous variable) pre-post intervention were
computed by paired t-test. These data are shown as
mean and 95 % condence interval. For triggers/clinical
variables analyses, the pre- and post-intervention periods
were set as the 4 weeks prior the 12-week intervention
period and the last 4 weeks of this intervention period,
respectively.
Descriptive statistics for trigger prole are expressed
as either group or whole cohort percentage, or group’s
sum. Comparisons in the proportion of triggers/patient
pre and post intervention were calculated by two-sided
Exact Fisher’s test. Data were computed in the SPSS
software (IBM, Version 19.0, Chicago, IL). A p value < 0.05
was considered statistically signicant.
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RESULTS
Twenty-ve participants were per-protocol analysed.
Table 1 shows participants clinical and anthropometrical
characteristics. In the whole cohort, 92 % of patients (23
out of 25 patients) reported at least one trigger during
the intervention period. The most common triggers
were stress/irritability (15/25 patients, or 60%), sleep
deprivation (15/25 patients, or 60%), fasting (7/25 patients,
or 28 %), food (7/25 patients, or 28 %), and odours (5/25
patients, or 20%). The groups’ trigger prole are shown
in the Figure 1. Most patients (13/25, or 52%) ascribed ≥ 3
triggers to their attacks in the baseline period.
The exercise group showed a higher baseline
proportion of patients with ≥ 3 triggers (69 %)
compared to waitlist group (25 %) (p = 0.041)
(Figure 2). After intervention period, the exercise
group showed reduced migraine attack frequency
compared to waitlist group [mean (CI 95 %): exercise
= -2.5 (-3.7, -1), p = 0.002 vs waitlist = 0.9 (2.4, -0.8), p =
0.341], while there was no difference in the proportion
of patients with ≥ 3 triggers between waitlist (16.6 %)
and exercise (30 %) groups (p = 0.502) (Figure 2). The
exercise group showed greater numeric reductions
(i.e., “Δ” values computed from group’s sum) than
waitlist group for the triggers stress/irritability (-14
vs -9), fatigue (-12 vs -6), and menstruation (-9 vs -5)
(Figure 3).
Figure 4 illustrates the ow of migraine triggers for
each group across time from baseline to post intervention
period. Triggers that were not reported by patients in
any period of intervention were designated “no trigger”.
DISCUSSION
To our knowledge, this is the rst study to evaluate
the triggers prole of migraine patients following exercise
training. In this secondary analysis, we tracked back the
triggers’ prole of a migraine patient cohort enrolled in
a randomized control trial testing the efcacy of aerobic
exercise training for migraine prevention. We intended to
identify possible changes in the pattern of trigger prole
following the aerobic exercise training protocol.
Variables Waitlist Exercise
Age (years) 34.2±9.0 37.4±13.8
Body Mass (kg) 69.6±18.9 72.9±15.7
Height (m) 1.63±0.1 1.64±0.05
BMI (kg/m
2
) 25.9±6.03 27.0±4.5
Sex:
Male, n(%) 3(25) 2(15.4)
Female, n(%) 9(75) 11(84.6)
Time living with migraine (yrs.) 15.6±8.5 18.2±13.3
Days w/ Migraine (n/month) 7.6±.4 8.9±3.6
Attacks Frequency (n/month) 5.1±2.5 6.3±3
Table 1. Participants’ characteristics. Data expressed as
mean ± standard deviation, or group’ percentage.
Figure 1. Trigger prole observed in waitlist and exercise groups.
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Figure 2. Triggger prole before and after exercice.
Figure 3. Change in common migraine triggers after intervention period.
We conrmed previous studies showing a high
percentage of patients reporting at least one trigger
(over 90 %)
9
, as well as we replicated the data showing
perceive stress, sleep deprivation, and fasting (skipping
meals) as the most common triggers
9–13
. We found that
the higher proportion of patients with ≥ 3 triggers in the
exercise group compared to waitlist group at baseline
equalized the waitlist group after intervention period
(Figure 2), probably reecting the reduction in the
number of migraine attacks across time with exercise
training. This also seemed to be the case regarding
the greater numeric reduction for most triggers in the
exercise group (Figure 3). Moreover, this larger numeric
reduction for some triggers in the exercise group could
be due to a greater sample size in this group.
While regular aerobic exercise may reduce migraine
frequency
1,3
, between 1/4 and 1/3 of migraine patients
report physical exercise as a consistent trigger
14,15
.
Surprisingly, there was no reported physical exercise-
triggered attack in this study. Some explanations to this
nding may be the fact that all participants were willing to
participate in an exercise program, the exercise intensity
was gradually increased up to the level prescribed
(moderate intensity around 70% of the age-predicted
maximum heart rate) based on cardiorespiratory
parameters, and all exercise sessions were supervised.
It is relevant to understand the relation of triggers
with physical exercise, since there is no specic exercise
prescription recommendation for migraine patients with
regard to their personal trigger prole, or whether or not
the surge of new popular exercise modalities could be
deleterious for the migraine patient. For example, new
popular exercise modalities that rapidly gain adepts
worldwide such as high intensity interval training
19
or training in a fasted state
20
, can be challenging for a
migraine patient and is impractical to be recommended.
On the other hand, in face of positive metabolic and
cardiovascular benet of these exercise modalities,
one could question whether a progressive introduction
of such exercise types would benet clinical aspects
of migraine, including the trigger pattern. Such trigger
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Headache Medicine, v.10, n.1, p.10-15, 2019
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Figure 4. Flow of migraine triggers for each group
across time from baseline to post intervention period.
analysis, in clinical practice, could help patients to detect
either positive or potentially harmful effects of regular
physical activity interacting with subjective triggers. In
the future, further studies could establish specic exercise
prescription recommendations for this population.
Although the data here do not allow us to draw
conclusion for specic effects of exercise training on
the pattern of migraine triggers, regular aerobic exercise
training mediates several neurdocrine, neuroimmune,
and neuromodulatory processes, which could be
accounted for the greater reduction in triggers such as
stress/irritability, sleep deprivation, menstruation, neck
pain, and fatigue in the intervention group. For example,
regular exercise is thought to promote anti-inammatory
effects
21
, regulate the hypothalamic-pituitary-adrenal
axis mediating habituation of stress response
22–24
, which
are akin with the recent evidence of exercise-mediate
anxiolysis and lower pro-inammatory cytokines in
migraine women
7
. Also, aerobic exercise may improve
sleep quality, and therefore could prevent sleep
deprivation-triggered attacks, by changing melatonin
production
25,26
, which in its turn represent a endogenous
molecule thought to play a role in the pathomechanisms
of migraine disorders
27
. A recent study showed that
aerobic exercise helped to reduce neck pain in a particular
subpopulation of patients presenting with both migraine
and tension-type headaches
28
. Less attacks due to
fatigue could reect improvement in oxidative energy
metabolism following exercise training through changes
in mitochondrial function, which has been also linked to
migraine pathophysiology
29,30
.
There was a large difference in non-identiable
triggers between groups (20 attacks). It is likely that
interference from attention and care delivered by
researchers to the exercise group during the exercise
sessions may have rendered participants more aware of
their triggers by speaking with researchers about their
personal clinical features.
Limitations and Strengths
There are limitations in this study, which hamper one
to generalise our ndings. The study is comprised of a
small sample of patients interested in adopting aerobic
exercise training as a non-pharmacological approach to
manage their migraine. This constitute selection bias and,
thus, this sample do not represent the general migraine
population. Furthermore, this is a secondary, per-protocol
analysis, which means that the analyses were designed
after randomization. The strengths of this study lie on
the trigger data collected through paper-based diary
throughout the study period, and a supervised exercise
program design.
Taking into account multiple neurophysiological
and biochemical processes affected by physical exercise,
and possible relation to migraine triggers mechanisms,
further studies are needed to elucidate particular
clinical responses of aerobic exercise training in a more
representative sample.
CONCLUSIONS
The preventive effect of regular aerobic exercise
may reect on the triggers pattern of patients. Mostly by
reducing the number of triggers, and the more frequent
ones. Tracking the patient triggers prole during exercise
training interventions may unravel specic clinical data,
and further advance the understanding of the relationship
between exercise and migraine. The implications on
exercise prescription should be further explored in the
future.
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Headache Medicine, v.10, n.1, p.10-15, 2019
Acknowledgements: The authors are grateful to
the whole staff of the Centre for Studies on Exercise
Psychobiology and to all patients.
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