Exercise-Induced Change in Plasma IL-12p70 Is Linked to Migraine Prevention and Anxiolytic Effects in Treatment-Naïve Women: A Randomized Controlled Trial

Abstract

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.

Non‐Pharmacological Treatment for Primary Headaches Prevention and Lifestyle Changes in a Low‐Income Community of Brazil: A Randomized Clinical Trial

“…We confirmed the preventive effect of either relaxation 7,10 or aerobic exercise 14,16 to reduce the number of headache days, or the combination of both interventions to reduce headache intensity. 13 This may reflect a synergistic effect of these interventions, which may involve common protective mechanisms.…”

“…13 This may reflect a synergistic effect of these interventions, which may involve common protective mechanisms. Putative mechanisms that have been ascribed for reduced headaches may include immunomodulation through the balance of pro-/antiinflammatory immune mediators (eg, cytokines), 14,16,37 modulation of the autonomic nervous system (eg, increased parasympathetic/decreased sympathetic tone), 16,38 and neuroendocrine regulation of stress response (eg, facilitation/habituation of hypothalamic-pituitary-adrenal axis). 39,40 This study did not provide evidence for reduction on perceived stress, and whether possible reductions on this variable would be related to lower headache frequency and intensity.…”

“…3 Even in the public health system of developed metropolitan areas in Brazil, nearly 30% of patients do not receive any headache preventive treatment. [6][7][8] Promoting health behavior and lifestyle changes, including management of perceived stress through relaxation, [6][7][8][9][10][11] and increase physical activity levels through aerobic exercise, [12][13][14][15][16] has been shown to be effective to improve clinical outcomes in primary headache disorders. [6][7][8] Also, such approaches may promote health behavior such as increased physical activity, albeit studies have been limited to tertiary clinics settings.…”

“…[6][7][8] Also, such approaches may promote health behavior such as increased physical activity, albeit studies have been limited to tertiary clinics settings. [6][7][8] Promoting health behavior and lifestyle changes, including management of perceived stress through relaxation, [6][7][8][9][10][11] and increase physical activity levels through aerobic exercise, [12][13][14][15][16] has been shown to be effective to improve clinical outcomes in primary headache disorders.…”

Antioxidant and cytokine levels in plasma of patients with attack and non-attack periods

“…In addition to the excessive ROS generation in migraine, cytokine generations such as interleukin (IL)-1beta (IL-1 and IL-6 are responsible in the etiology of migraine (Oliveira et al 2017a;Oliveira et al 2017b). As a member of cytokines, tumor necrosis factor-alpha (TNF-) is a key marker in the neuronal physiological process and progression of migraine (Sarchielli et al 2006;Yücel et al 2016;Martami et al 2018).…”