Introduction: Since endocannabinoids have been implicated in migraine pathophysiology, we conducted a randomized, controlled clinical trial to test the effects of a 12-week aerobic exercise intervention on plasma anandamide (AEA) and its relation with clinical, psychological, and cardiorespiratory outcomes. Materials and Methods: Episodic migraine patients taking no preventive drugs and nonheadache individuals were recruited from Hospital São Paulo and a tertiary headache clinic between March 2012 and March 2015. Participants were randomly assigned to receive aerobic exercise or enter the waitlist. Primary outcome was changes in plasma AEA; secondary outcome was number of days with migraine/month; and other clinical variables, mood scores, and cardiorespiratory fitness were chosen as tertiary outcomes. Measurements were taken on headache-free days. Data were analyzed by generalized linear models. Discussion: Fifty participants concluded the study (mean±SD age=36.2±10.9, and BMI=26.5±4.5). The plasma AEA reduced in migraine exercise (p<0.05) and control exercise groups (p<0.01). The number of days with migraine (p<0.01), migraine attacks (p<0.05), and abortive medication used (p<0.05) reduced in the migraine exercise group, whereas cardiorespiratory fitness increased in migraine exercise and control exercise groups (both p<0.05). Anxiety, depression, anger, and fatigue scores improved in the migraine exercise group (p<0.05 for all). Significant correlations between reduction in abortive medication used and cardiorespiratory fitness (r=−0.81 p<0.001), and reduced AEA (r=0.68 p<0.05) were found. Conclusions: This study suggests that peripheral AEA metabolism may be partly linked to the clinical and cardiorespiratory benefits of regular aerobic exercise in migraine patients. Trials registration: #NCT01972607.

Migraine diagnosis is based on clinical aspects and is dependent on the experience of the attending physician. This study aimed to describe the patients journey profile until they start their experience in a tertiary headache center. In a cross-sectional study, medical charts from migraine patients were reviewed to describe which treatments, procedures and follow-up strategies are performed until the first appointment with a headache specialist. Patients from both sexes, ≥18 years old, which came to their first visit from March to July 2017 were included. Sociodemographic information, headache characteristics, diagnostic methods previously used, clinical history, family history and the treatments previously used were assessed in the first appointment with a specialist. Patient Health Questionnaire-9 and General Anxiety Disorder-7 were also applied. Descriptive analyses were performed to describe the sample profile and statistical tests were used to evaluate factors associated with the type of migraine (chronic or episodic). The sample consisted of 465 patients. On average, the pain started 17.1 (SD = 11.4) years before the first appointment with a headache specialist. Most of patients were classified as having chronic migraine (51.7%), with an average frequency of 15.5 (SD = 9.9) days per month. Regarding patients’ journey until a specialist, most patients were submitted to laboratory tests (74.0%), cranial tomography (66.8%) and magnetic resonance imaging (66.8%) as diagnostic methods, and preventive drugs (70.2%) and acupuncture (61.0%) as treatments. After stratification by migraine type as episodic or chronic, patients with chronic migraine were submitted to more magnetic resonance imaging test, acupuncture, psychotherapy, used preventive drugs, and reported to have used topiramate without beneficial effects. Brazilian patients with migraine experiment a long journey until getting to a headache specialist and are submitted to a great number of unnecessary exams, especially those with chronic migraine.

Objective: To conduct a randomized controlled trial to evaluate the effect of a 12-week aerobic exercise program for migraine prevention, plasma cytokines concentrations (TNF-α, interleukin [IL]-1β, IL-6, IL-8, IL-10, and IL-12p70), and anxiety in women with migraine. Methods: Women with episodic migraine (ICHD-II), aged between 20 and 50 years, who had never taken any prophylactic medication, and were physically inactive in the past 12 months were recruited from the university’s hospital and a tertiary headache clinic between March 2012 and March 2015. Migraine attacks were recorded in headache diaries, cytokines were quantified by flow cytometry, and anxiety was assessed by the 7-item General Anxiety Disorder (GAD-7) scale. Blood sampling and psychometric interviews were undertaken on headache-free days. Results: Twenty participants ([mean ± SD] age 33.8 ± 10.5; BMI 26 ± 5.2) were randomly assigned and received intervention (“trained”: n = 10) or entered on a waitlist (“inactive”: n = 10). There were no differences between groups regarding patients’ characteristics and baseline data. Days with migraine (p = 0.001), IL-12p70 levels (p = 0.036), and GAD-7 score (p = 0.034) were significantly reduced in the trained group after the intervention period, but there were no significant changes in these variables in the inactive group. There was no change in the levels of the other cytokines in either group. There were positive correlations between a reduction in IL-12p70 level and a reduction in the number of days with migraine (R2 = 0.19, p = 0.045), and GAD-7 score (R2 = 0.53, p < 0.001). Conclusion: The clinical and psychological therapeutic effects of aerobic exercise in treatment-naïve women with migraine may involve the downregulation of IL-12p70.

Background: Physical inactivity has been linked to headache disorders but estimates based on the current World Health Organization physical activity guidelines are unknown. Objective: To test the associations between headache disorders and physical inactivity in the ELSA-Brasil cohort. Methods: In a cross-sectional analysis, linear (continuous variables) and logistic regression models (categorical variables) tested the associations of physical activity levels in the leisure time, commuting time, and combined leisure time physical activity + commuting time physical activity domains with headache disorders, adjusted for the effects of sociodemographic data, cardiovascular risk variables, psychiatric disorders, and migraine prophylaxis medication. Results: Of 15,105 participants, 14,847 (54.4% women) provided data on physical activity levels and headache. Higher physical activity levels (continuous values) in the leisure time physical activity domain associated with lower migraine and tension-type headache occurrence and lower headache attack frequency, while in the commuting time physical activity domain it associated with more frequent headache attacks. Compared to people who met World Health Organization physical activity levels in the leisure time physical activity or combining leisure time physical activity + commuting time physical activity domains (i.e. ≥150 min.wk⁻¹ of moderate and/or ≥75 min.wk⁻¹ of vigorous physical activity), physical inactivity associated with higher migraine occurrence, while somewhat active (i.e. not meeting World Health Organization recommendations) associated with higher migraine and tension-type headache occurrence. Physical inactivity in the commuting time physical activity domain associated with higher tension-type headache in men and lower migraine in women. Physical inactivity within vigorous leisure time physical activity intensity, but not moderate leisure time physical activity, associated with higher migraine, mostly in women. Finally, physical inactivity associated with higher headache attack frequency regardless headache subtype. Conclusion: Physical inactivity and unmet World Health Organization physical activity levels associate with primary headaches, with heterogeneous associations regarding headache subtype, sex, physical activity domain/intensity, and headache frequency in the ELSA-Brasil study.