The present study tested the effectiveness of jogging, eye movement exercises, and diaphragmatic breathing in patients with migraine pain. The first experimental group received jogging plus eye movement exercises and the second experimental group received jogging plus diaphragmatic breathing, whereas the control group only received treatment as usual. The results showed significant effects of the interventions on the patients' symptoms in the experimental groups (Fig. 4 and Table 3). Therefore, regular aerobic exercises (i.e., jogging) and practicing body-mind awareness (i.e., eye movement exercises and diaphragmatic breathing) appear to elucidate the negative effects of stressful insults in the brain, on the body muscles, respiratory rate and depth, and the flow of biomolecules and hormones (i.e., Nitric Oxide (NO), brain-derived neurotrophic factor (BDNF), and adenosine monophosphate-activated protein kinase (AMPK)). These effects could stem from various possible mechanisms, including (a) brain-gut and neuroimmune axis (e.g., hypothalamus-pituitary-adrenal (HPA); (b) brain-brain reciprocal interlinks (e.g., hippocampus-anterior cingulate cortex and medial-prefrontal cortex (mPFC) oscillations); and (c) circadian disruption and biomolecular dysregulation (e.g., oxidative stress and neurogenic inflammation), each of which may play a key initiating role in spurring migraine-related symptoms (75–78).
Although the results of a meta-analysis (29) suggested that the effect of aerobic exercise on patients with migraine is only related to the frequency of the attacks, in a recent study (79), aerobic exercises are assumed to influence all aspects of migraine pain including frequency, duration, and intensity. The paradoxical findings in the literature on the effectiveness of aerobic exercise could be related to the following reasons. First, based on the International Headache Society (IHS) recommendations (69, 80), one major drawback of previous studies is heterogeneity in applying headache-related outcome measures. Second, some studies have failed to adequately address issues related to blinding, sample size, designing, and randomization. Third, no study has compared the outcomes of aerobic exercises on patients with migraine without aura (MwoA) and patients with migraine with aura (MwA). Forth, evidence was scarce for comparing the outcomes of aerobic exercises and pharmacological treatment of migraine pain. Fifth, in no study so far aerobic exercise has been complemented with another non-medication intervention; therefore, this was the first study that, based on findings from the migraine brain studies, combined jogging with eye movement exercises or diaphragmatic breathing to decrease kinesiophobia or sensitivity to movements in migraine patients (81, 82).
As a diagnostic criterion, patients with migraine have a fear of movement or kinesiophobia (83–85). To develop readiness for and potentiate neural responsiveness to a full-body exercise and to improve body awareness (65, 66), the present study provided the patients with eye movement exercises or diaphragmatic breathing (86–88). Considering the neural or Hebbian learning, stimulating brain on a regular basis adjusts brain functions at the molecular level (e.g., signaling mechanisms and memory formation) (89). Eye movement exercises are identified to activate widespread, interconnected cortical and subcortical networks such as superior colliculus, oculomotor network (ON) in the brain stem, dorsolateral prefrontal brain cortex, basal ganglia, subthalamic structures, substantia nigra pars reticulata, visuo-motor, parietal, and posterior cingulate cortices (90–94). Each of these networks plays an excitatory or inhibitory role in pain processing (95, 96). Therefore, performing eye movement exercises on a regular basis stimulates or potentiates almost all major parts of the brain that are important in the experience of the pain. The corneoretinal potential (CRP) transduction by eye movement exercises is a bioelectrical signal, which is produced by two modes of polarities during eye movement exercises: a positively charged end (cornea) and a negatively charged end (retina) (97). The conjugated eye movement exercises (i.e., from right to left or from top to bottom and the vice versa) transduces sequential negative or positive electrical charges on the retina (98). These types of training-induced transduction should potentiate synaptic plasticity and facilitate myelination mechanisms by (a) regulating signal transmission (i.e., neuromodulation of ion channels and neurotransmitters); (b) synchronizing oscillations (i.e., frequency, amplitude, or phase); and (c) cortical reorganization or enhancement of timing within related cortical-cortical or cortical-subcortical brain networks (i.e., enhancement of memory, visuospatial accuracy, decision-making, or task switching) (99–103).
In the present study, another essential guided behavior was diaphragmatic breathing.
In the present study, another essential guided behavior was diaphragmatic breathing. It should be noted that jogging itself may increase exercise-induced stress insults in migraine brain; however, diaphragmatic breathing helps with promoting stress-response control indices and potentiating cortical readiness prior to jogging (
104,
105). Diaphragmatic breathing can improve brain function via the following mechanisms: (a) chemical, which involves the regulation of biomolecules such as adenosine, melatonin, orexin, or calcitonin-gene-related peptide (CGRP); (b) mechanical, which involves enhancing the rate, length, or intensity of breathing at the cortical level; and (c) cortical-subcortical control, which is related to shared breathing centers and headache-related networks such as brainstem and medullary centers (
106–
109). Together, jogging, eye movement exercises, and diaphragmatic breathing may induce mitochondrial oxidative phosphorylation, electrical transduction, ionic, and biomolecule homeostasis that can explain primary and secondary outcomes of the present study.
All participants in the present study were female patients with episodic migraine. This may limit the generalizability of our findings to male patients with migraine. Subsequently, the same study should be also conducted with male migraine patients. Moreover, heterogeneity in the rate of prescribed and OTC medication use in the control group was another limitation of the present study. Moreover, we did not ask patients in the control group to keep a journal of any medication that they were taking for their pain because, there is no single or specific medication with consistent or long-term effect for migraine, hence even recording the rate of medication use over a two-year by the patients in the control group deemed an unviable goal and could not help with interpreting the study outcomes. Furthermore, given that the present study was conducted in a Middle Eastern country with a different environment and culture, future studies can replicate the study with patients from different cultural, racial, and ethnical backgrounds. Future studies can also examine the outcomes of the present interventions for other types of headache, migraine-related comorbidities (e.g., epilepsy, tinnitus, chronic dizziness or vertigo, sleep apnea, or restless leg syndrome), and even for psychopathologies like depression and anxiety.