Possible mechanisms of auricular acupoint stimulation in the treatment of migraine by activating auricular vagus nerve. / 从耳迷走神经探讨耳穴治疗偏头痛的可能机制.

Under the guidance of traditional Chinese medicine theory, the clinical research of auricular acupoint stimulation in the treatment of migraine has gained a lot, and the curative efficacy is definite, but its mechanism remains unclear. In the present paper, we discussed the efficacy of auricular acupoint stimulation including "transcutaneous auricular vagus nerve stimulation" (taVNS) in the treatment of migraine in recent years. Through bibliometric analysis, we screened out top 10 auricular acupoints (Shenmenï¼»TF4ï¼½, Pizhixiaï¼»AT4ï¼½, Jiaoganï¼»AH6aï¼½, Ganï¼»CO12ï¼½, Yidanï¼»CO11ï¼½, Neifenmiï¼»CO18ï¼½, Shenï¼»CO10ï¼½, Nieï¼»AT2ï¼½, Zhenï¼»AT3ï¼½ and Eï¼»AT1ï¼½) which were the most frequently used for migraine. Majority of these auricular acupoints just distributed in the region innervated by auricular vagus nerve. Thus, we thought that the analgesic effect of needling these auricular acupoints for migraine was produced by triggering the auricular vagus nerve, and concluded that the central mechanism underlying induction of analgesic effect by activating auricular vagus nerve may be achieved by activating the descending pain regulation pathway of the locus coeruleus nucleus and dorsal raphe nucleus. In addition, taVNS-induced 1) regulation of the activities of brain's default network and pain matrix, 2) activation of the cortical descending pain regulation pathway, and 3) inhibition of the neuroinflammatory response may also contribute to its ameliorating effect of migraine. This paper may provide ideas for the future research on the mechanism of auricular acupoint treatment of migraine.

The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines.

The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (- 6.45 ± 0.82 mg/dl vs - 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (- 2.02 ± 0.30 ng/ml vs - 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P < 0.001), frequency (P = 0.001), headache impact test (HIT-6) (P < 0.001), headache dairy results (HDR) (P = 0.003), and migraine headache index score (MHIS) (P < 0.001) had significantly decreased in the intervention as compared to the control group. No significant changes were observed for NO levels and duration of migraine pains. ALA supplementation can be considered a potential adjunct treatment in patients with migraine due to its improving mitochondrial and endothelial functions and clinical symptoms.

Ginger for Migraine.

Many preclinical and clinical studies have examined the potential benefits of ginger extracts for a range of medical disorders. Ginger has been found to reduce both pain and nausea and has therefore also been studied in the context of migraine headache. One randomized controlled trial (RCT) found that ginger was no better than placebo for the prevention of migraine episodes. One meta-analysis (pooled N = 227) found that, relative to placebo, ginger was associated with a higher proportion of patients who were pain free 2 hours after treatment (risk ratio [RR], 1.79; 95% confidence interval [CI], 1.04-3.09; 2 RCTs). In this meta-analysis, relative to placebo, ginger reduced the risk of migraine-related nausea and vomiting (RR, 0.48; 95% CI, 0.30-0.77; 3 RCTs) and was not associated with an increased risk of adverse events (RR, 0.80; 95% CI, 0.46-1.41; 3 RCTs). No other RCT data are available. Such an evidence base is clearly too small for formal recommendations to be possible. It is suggested that raw ginger or proprietary ginger extracts may be useful as a home remedy for patients who experience an episode of migraine and who, for whatever reason, cannot take established first-line treatments for acute migraine. How ginger thus used compares with established treatments for migraine is presently unknown. Finally, it must be remembered that the chemical constituents of ginger will vary across source and extract; so, when an extract of ginger is studied, the findings of the study can be generalized only to that extract and, possibly, to other extracts with a similar composition.

Migraine and Sleep-An Unexplained Association?

Migraine and sleep disorders are common chronic diseases in the general population, with significant negative social and economic impacts. The association between both of these phenomena has been observed by clinicians for years and is confirmed by many epidemiological studies. Despite this, the nature of this relationship is still not fully understood. In recent years, there has been rapid progress in understanding the common anatomical structures of and pathogenetic mechanism between sleep and migraine. Based on a literature review, the authors present the current view on this topic as well as ongoing research in this field, with reference to the key points of the biochemical and neurophysiological processes responsible for both these disorders. In the future, a better understanding of these mechanisms will significantly expand the range of treatment options.

Effect of Vitamin D and/or Marine n-3 Fatty Acid Supplementation on Changes in Migraine Frequency and Severity.

BACKGROUND: There is interest in whether supplements, including vitamin D and marine omega-3 (n-3) fatty acids, may be effective migraine prophylaxis. However, few studies have evaluated whether vitamin D or n-3 fatty acid supplementation may reduce migraine frequency or severity. METHODS: Participants in the VITamin D and OmegA-3 TriaL (VITAL) were assigned to vitamin D3 (2000 IU/d) or marine n-3 fatty acid (1 g/d) supplementation in a 2-by-2 factorial design. Lifetime history of migraine was assessed a median of 4.6 years after the start of the trial. Individuals were asked to self-report changes in migraine frequency (no change, more frequent, or less frequent) and severity (no change, more severe, less severe) in the past 5 years. We used χ2 tests to compare proportions of individuals reporting changes in migraine frequency and severity between active and placebo groups. RESULTS: Among the 25,871 participants in VITAL, 1032 participants had a history of probable migraine and provided information on changes in migraine frequency and severity. The percentage of individuals reporting decreases in migraine frequency did not differ between active (69.0%) and placebo vitamin D (68.4%) (P value = 0.54) or between active (67.8%) and placebo n-3 fatty acid (69.6%) (P value = 0.82). Similarly, the percentage of individuals reporting decreases in migraine severity did not differ between active (64.1%) and placebo vitamin D (65.0%) (P value = 0.86) or between active (64.5%) and placebo n-3 fatty acid (64.5%) (P value = 0.96). CONCLUSIONS: Neither vitamin D nor marine n-3 fatty acid supplementation, compared to placebo, affected migraine frequency or severity among middle-aged or older adults.

Review of aromatherapy essential oils and their mechanism of action against migraines.

ETHNOPHARMACOLOGICAL RELEVANCE: Migraines have become a major threat to human health, as they significantly affect human health and quality of life due to a high prevalence rate, attack rate and pain intensity. Aromatherapy, with its comfortable and pleasant natural characteristics and rapid and efficient characteristics, is widely favored by patients in the folk. Chinese folk also have the application history and related records of aromatic plants in the treatment of migraine. AIM OF THE STUDY: This study was conducted to review the pathogenesis of migraine, the application of plant essential oils in the treatment of migraine, and further explore the material basis and mechanism of action of plant essential oils against migraine. MATERIALS AND METHODS: Search the electronic literature of essential oils with anti-migraine effect in Google Scholar, PubMed and China National Knowledge Infrastructure, and further search the research situation of the monomer components of essential oils in migraine, inflammation, pain and other aspects. RESULTS: studies show that there are 10 types of plant essential oils that could relieve migraine symptoms, and that 16 monomers may play a role in migraine treatment by effectively inhibiting neurogenic inflammation, hyperalgesia and balancing vasorelaxation. CONCLUSION: Aromatic plant essential oils can relieve migraine effectively, these findings can be used as an important part of the development of anti-migraine drugs.

Experience of migraine, its severity, and perceived efficacy of treatments among cannabis users.

OBJECTIVES: As the legal and cultural landscape surrounding cannabis use in the United States continues to evolve, more Americans are turning to cannabis to self-medicate a number of ailments, including migraines. The purpose of the present study was to examine patterns of cannabis use and its associated relief among migraineurs. DESIGN: Participants were N = 589 adult cannabis users living in states with full legal access. Using a cross-sectional design, participants completed an online survey assessing their cannabis use profiles, migraine experience, and self-reported relief from cannabis and non-cannabis treatments. RESULTS: 161 participants (27.3 %) reported experiencing migraines. 76.4 % of migraineurs (N = 123) endorsed using cannabis to treat their migraines. 69.9 % (N = 86) of migraineurs using cannabis for migraine relief also endorsed using non-cannabis products (e.g., over-the-counter pain medication, triptans) to treat their migraines. Although their subjective health was similar (p = .17), migraineurs who endorsed using cannabis to treat their migraines reported more severe migraines compared to those who did not (p = .02). Migraineurs reported significantly more migraine relief from cannabis compared to non-cannabis products, even after controlling for migraine severity (p = .03). The majority of migraineurs using cannabis to treat their migraines were not medical cardholders (65.0 %), suggesting that these individuals were self-medicating in lieu of physician guidance. CONCLUSIONS: The present study provides insight into the prevalence of cannabis use for migraine relief in a sample of cannabis users, and suggests that these migraineurs experience a high level of migraine relief from cannabis. Future studies are needed to determine the cannabis forms, potencies, and dosages that are most effective at treating migraine pain.

Progress in Traditional Chinese Medicine for the Treatment of Migraine.

Migraine is a recurrent disease with complex pathogenesis and is difficult to cure. At present, commercially available western migraine drugs are prone to generate side effects while treating the disease. Traditional Chinese medicine (TCM) avoids side effects via treatment with the principles of "treating both symptoms and root causes", "overall adjustment", and "treatment based on syndrome differentiation". Three strategies of drug treatment were developed based on the syndromes, i.e., removing stasis, calming liver Yang, and reinforcing deficiency. Prescriptions of removing stasis mostly contain Chuanxiong rhizome (Chuan Xiong) to remove blood stasis by promoting blood circulation and improve properties of hemorheology, and Da Chuan Xiong Formula (DCXF) is a traditional prescription widely used in clinical practice. Prescriptions of calming liver Yang usually take Ramulus Uncariae cum Uncis (Gou Teng) as the main herb, which can calm the liver Yang via improving vasomotor function, and Tian Ma Gou Teng Decoction (TMGTD) is the representative drug. For reinforcing deficiency, Chinese doctors frequently utilize Angelica Sinensis (Dang Gui) and Astragali Radix (Huang Qi) to nourish blood and Qi in order to improve the weak state of human body; Dang Gui Bu Xue Decoction (DGBXD) is the commonly used prescription. These strategies not only treat the symptoms of diseases but also their root causes, and with the features of multiple targets, in multiple ways. Therefore, TCM prescriptions have obvious advantages in the treatment of chronic diseases such as migraine. In this review, we provided an overview of the pathogenesis of migraine and the function of representative TCM preparations in therapy of migraine as well as the mechanism of action according to effective researches, in order to provide reference and clue for further researches.

Noninvasive Neuromodulation in Migraine.

PURPOSE OF REVIEW: The past two decades has seen an influx of noninvasive neuromodulation devices aimed at treatment of various primary headache disorders, including cluster headache and migraine. This narrative review is to summarize the current options in noninvasive neuromodulation in migraine. RECENT FINDINGS: A variety of noninvasive neuromodulation devices have been FDA cleared and marketed for use in migraine, including single-pulse transcranial magnetic stimulation (sTMS), noninvasive vagal nerve stimulators (nVNS), and external trigeminal nerve stimulators (eTNS). Newer devices include peripheral electrical stimulation devices (PES), caloric stimulation, and others. Each has varying levels of evidence supporting its use in migraine, tolerability profiles, and access issues. Noninvasive neuromodulation devices can be beneficial when used in patients with migraine, with minimal side effects. As more devices are developed, approved, and marketed in the future, rigorous research on efficacy and safety remain a top priority.

Pharmacological options for the treatment of chronic migraine pain.

Migraine is a debilitating neurological condition with symptoms typically consisting of unilateral and pulsating headache, sensitivity to sensory stimuli, nausea, and vomiting. The World Health Organization (WHO) reports that migraine is the third most prevalent medical disorder and second most disabling neurological condition in the world. There are several options for preventive migraine treatments that include, but are not limited to, anticonvulsants, antidepressants, beta blockers, calcium channel blockers, botulinum toxins, NSAIDs, riboflavin, and magnesium. Patients may also benefit from adjunct nonpharmacological options in the comprehensive prevention of migraines, such as cognitive behavior therapy, relaxation therapies, biofeedback, lifestyle guidance, and education. Preventative therapies are an essential component of the overall approach to the pharmacological treatment of migraine. Comparative studies of newer therapies are needed to help patients receive the best treatment option for chronic migraine pain.

The role of acupuncture in the treatment of chronic pain.

Acupuncture is a practice based on traditional Chinese medicine, in which needles are used to restore the body's internal balance. Recently, there has been growing interest in the use of acupuncture for various pain conditions. Acupuncture's efficacy in five pain conditions-low back pain (LBP), migraines, fibromyalgia, neck pain, and abdominal pain-was evaluated in this evidence-based, comprehensive review. Based on the most recent evidence, migraine and fibromyalgia are two conditions with the most favorable outcomes after acupuncture. At the same time, abdominal pain has the least evidence for the use of acupuncture. Acupuncture is efficacious for reducing pain in patients with LBP, and for short-term pain relief for those with neck pain. Further research needs to be done to evaluate acupuncture's efficacy in these conditions, especially for abdominal pain, as many of the current studies have a risk of bias due to lack of blinding and small sample size.

Impact of coronavirus disease 2019 (COVID-19) pandemic on patients with migraine: a web-based survey study.

BACKGROUND: Since the declaration COVID-19 as a pandemic, healthcare systems around the world have faced a huge challenge in managing patients with chronic diseases. Patients with migraine were specifically vulnerable to inadequate medical care. We aimed to investigate the "real-world" impact of COVID-19 pandemic on migraine patients, and to identify risk factors for poor outcome. METHODS: We administered an online, self-reported survey that included demographic, migraine-related, COVID-19-specific and overall psychosocial variables between July 15 and July 30, 2020. We recruited a sample of patients with migraine from headache clinic registry and via social media to complete an anonymous survey. Outcomes included demographic variables, change in migraine frequency and severity during the lockdown period, communication with treating physician, compliance to migraine treatment, difficulty in getting medications, medication overuse, symptoms of anxiety and/or depression, sleep and eating habits disturbance, screen time exposure, work during pandemic, use of traditional medicine, effect of Botox injection cancellation, and overall worries and concerns during pandemic. RESULTS: A total of 1018 patients completed the survey. Of the respondents, 859 (84.3%) were females; 733 (71.9%) were aged 20 to 40 years, 630 (61.8%) were married, and 466 (45.7%) reported working during the pandemic. In comparison to pre-pandemic period, 607 respondents (59.6%) reported increase in migraine frequency, 163 (16%) reported decrease in frequency, and 105 (10.3%) transformed to chronic migraine. Severity was reported to increase by 653 (64.1%) respondents. The majority of respondents; 626 (61.5%) did not communicate with their neurologists, 477 (46.9%) reported compliance to treatment, and 597 (58.7%) reported overuse of analgesics. Botox injections cancellation had a negative impact on 150 respondents (66.1%) from those receiving it. Forty-one respondents (4%) were infected with COVID-19; 26 (63.4%) reported worsening of their headaches amid infection period. Sleep disturbance was reported by 794 (78.1%) of respondents, and 809 (79.5%) reported having symptoms of anxiety and/or depression. CONCLUSIONS AND RELEVANCE: COVID-19 pandemic had an overall negative impact on patients with migraine. Several risk factors for poor outcome were identified. Long-term strategies should be validated and implemented to deliver quality care for patients with migraine, with emphasis on psychosocial well-being.

Central effects of erenumab in migraine patients: An event-related functional imaging study.

OBJECTIVE: To determine whether erenumab, a new monoclonal antibody to the calcitonin gene-related peptide (CGRP) receptor, exerts functional central effects in migraineurs by performing functional imaging scans on patients treated with erenumab. METHODS: We conducted an fMRI study on 27 patients with migraine using a well-established trigeminal nociceptive paradigm, examining patients before and 2 weeks after administration of the CGRP receptor antibody erenumab 70 mg. RESULTS: Comparing both visit days in all patients (n = 27) revealed that erenumab leads to a decrease in activation in the right thalamus (i.e., contralateral to the stimulated side), right middle temporal gyrus, right lingual gyrus, left operculum, and several clusters on both sides of the cerebellum. Furthermore, when responders (n = 9) and nonresponders (n = 8) of the respective same headache state were compared, we found a significant reduction of hypothalamic activation after the administration of erenumab in responders only (t = 4.78; contrast estimate 29.79 [90% confidence interval 19.53-40.05]). This finding of reduced hypothalamic activation was confirmed when absolute headache days was used as a regressor. INTERPRETATION: These findings suggest that erenumab may not be an exclusively peripheral migraine treatment but has additional central effects. Whether this is due to secondary changes after peripheral modulation of sensory input or indeed represents a direct central mode of action is discussed.

Intrarater and Interrater Reliability of the Flexion Rotation Test and Cervical Range of Motion in People With Migraine.

OBJECTIVE: The aim of this study was to determine the reliability, standard error of measurement (SEM), and smallest detectable change (SDC) of the flexion rotation test (FRT) and cervical range of motion (CROM) assessed with the CROM device in individuals with and without migraine. METHODS: Twenty-five women with migraine (mean age, 35 years; standard deviation, 10 years) and 25 comparable headache-free women (mean age, 32 years; standard deviation, 11 years) participated in this study. C1/C2 mobility was assessed with the FRT, whereas global cervical range of motion was calculated using a CROM device. To assess the interrater reliability, tests were conducted on the same day at 20-minute intervals, by 2 independent assessors, and they were repeated after a 1-week interval by the same assessor to evaluate the intrarater reliability. The mean value of 3 repetitions was used to calculate the intraclass correlation coefficient ICC(2,k), SEM, and SDC. RESULTS: The intrarater reliability was excellent (ICC > 0.83), and interrater reliability ranged from substantial to excellent (ICC > 0.77) for the FRT. The SEM ranged from 2.44° to 2.85°, and the SDC from 6.78° to 7.9°. Intrarater and interrater reliability for cervical range of motion was substantial to excellent (ICC > 0.65), with the SEM ranging from 2.03° to 5.46° and the SDC from 5.6° to 15.14°. CONCLUSION: The results demonstrate that FRT and global cervical range of motion with a CROM device show high reliability in individuals with migraine. In addition, the SEM and SDC were relatively small. Both assessments can be used for clinical evaluation of the cervical spine in individuals with migraine.

A Paradoxical Vasodilatory Nutraceutical Intervention for Prevention and Attenuation of Migraine-A Hypothetical Review.

Studies suggest that migraine pain has a vascular component. The prevailing dogma is that peripheral vasoconstriction activates baroreceptors in central, large arteries. Dilatation of central vessels stimulates nociceptors and induces cortical spreading depression. Studies investigating nitric oxide (NO) donors support the indicated hypothesis that pain is amplified when acutely administered. In this review, we provide an alternate hypothesis which, if substantiated, may provide therapeutic opportunities for attenuating migraine frequency and severity. We suggest that in migraines, heightened sympathetic tone results in progressive central microvascular constriction. Suboptimal parenchymal blood flow, we suggest, activates nociceptors and triggers headache pain onset. Administration of NO donors could paradoxically promote constriction of the microvasculature as a consequence of larger upstream central artery vasodilatation. Inhibitors of NO production are reported to alleviate migraine pain. We describe how constriction of larger upstream arteries, induced by NO synthesis inhibitors, may result in a compensatory dilatory response of the microvasculature. The restoration of central capillary blood flow may be the primary mechanism for pain relief. Attenuating the propensity for central capillary constriction and promoting a more dilatory phenotype may reduce frequency and severity of migraines. Here, we propose consideration of two dietary nutraceuticals for reducing migraine risk: L-arginine and aged garlic extracts.

United States Patients' Perspective of Living With Migraine: Country-Specific Results From the Global "My Migraine Voice" Survey.

BACKGROUND: Migraine is associated with debilitating symptoms that can affect daily functioning. "My Migraine Voice" was a large, cross-sectional, multi-country online survey aimed at understanding disease burden directly from people with migraine. OBJECTIVE: This study reports on the social and economic impacts of migraine, specifically the impact on activities of daily living and the costs of migraine, from the point of view of people with migraine in the United States. METHODS: The online survey was administered to adults with a self-reported diagnosis of migraine who experienced 4 or more monthly migraine days each month for the previous 3 months. Prespecified screening quotas were used so that 90% of respondents reported current or past use of preventive migraine medication, 80% of whom switched treatment (ie, changed their prescribed preventive medication at least once). The remaining 10% were preventive treatment naïve (ie, never used any prescribed preventive medication). Burden of migraine on activities of daily living and caregivers (eg, functional limitations, fear of next migraine attack, sleep problems) and economic burden (eg, out-of-pocket costs, impact on work productivity using the validated work productivity and activity impairment questionnaire) reported by respondents from the United States are presented. Results are stratified by employment status, migraine frequency (chronic vs episodic migraine), and history of preventive treatment. RESULTS: Thousand hundred and one individuals with migraine from the United States responded to the survey. Respondents reported limitations completing daily activities during all migraine phases, including during the premonitory/aura and postdrome phases. Most (761/1101 (69%)) relied on family, friends, or others for help with daily tasks and reported being helped a median of 9 days (25th percentile 5 days, 75th percentile 15 days) within the last 3 months. Respondents with chronic migraine reported being helped for more days (median 10 days, 25th percentile 5 days, 75th percentile 23 days) in the last 3 months. Almost all (962/1101 (87%)) experienced sleep difficulties and 41% (448/1101) (48% (336/697) of those with 2 or more preventive treatment failures) were very or extremely fearful of a next migraine attack. Median (25th percentile, 75th percentile) monthly out-of-pocket costs of $90.00 ($30.00, $144.00) in doctor's fees (n = 504), $124.00 ($60.00, $234.00) in health insurance (n = 450), $40.00 ($20.00, $100.00) for prescriptions (n = 630), and $50.00 ($0.00, $100.00) for complementary therapies (n = 255) were reported. Those with 2 or more preventive treatment failures reported higher monthly out-of-pocket doctor fees (median $99.00 ($30.00, $150.00), n = 388). Among employed respondents (n = 661), migraine resulted in 22% absenteeism, 60% presenteeism, 65% work productivity loss, and 64% activity impairment. CONCLUSIONS: Migraine impacts individuals' activities of daily living, work-life, and financial status, especially individuals with high needs, namely those with 4 or more monthly migraine days and prior treatment failures. People with migraine are impaired during all migraine phases, experience fear of their next migraine attack and sleep difficulties, and pay substantial monthly out-of-pocket costs for migraine. Burden is even greater among those who have had 2 or more preventive treatment failures. Impacts of migraine extend beyond probands to caregivers who help people with migraine with daily tasks, employers who are affected by employee absenteeism, presenteeism, and reduced productivity, and society which is burdened by lost and reduced economic productivity and healthcare costs.

Short-latency afferent inhibition and somato-sensory evoked potentials during the migraine cycle: surrogate markers of a cycling cholinergic thalamo-cortical drive?

BACKGROUND: Short-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features. METHODS: SAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation. RESULTS: Compared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI. CONCLUSIONS: The migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.

Alleviation of migraine symptoms by application of repetitive peripheral magnetic stimulation to myofascial trigger points of neck and shoulder muscles - A randomized trial.

Migraine is a burdensome disease with an especially high prevalence in women between the age of 15 and 49 years. Non-pharmacological, non-invasive therapeutic methods to control symptoms are increasingly in demand to complement a multimodal intervention approach in migraine. Thirty-seven subjects (age: 25.0 ± 4.1 years; 36 females) diagnosed with high-frequency episodic migraine who presented at least one active myofascial trigger point (mTrP) in the trapezius muscles and at least one latent mTrP in the deltoid muscles bilaterally prospectively underwent six sessions of repetitive peripheral magnetic stimulation (rPMS) over two weeks. Patients were randomly assigned to receive rPMS applied to the mTrPs of the trapezius (n = 19) or deltoid muscles (n = 18). Whereas the trapezius muscle is supposed to be part of the trigemino-cervical complex (TCC) and, thus, involved in the pathophysiology of migraine, the deltoid muscle was not expected to interfere with the TCC and was therefore chosen as a control stimulation site. The headache calendar of the German Migraine and Headache Society (DMKG) as well as the Migraine Disability Assessment (MIDAS) questionnaire were used to evaluate stimulation-related effects. Frequency of headache days decreased significantly in both the trapezius and the deltoid group after six sessions of rPMS (trapezius group: p = 0.005; deltoid group: p = 0.003). The MIDAS score decreased significantly from 29 to 13 points (p = 0.0004) in the trapezius and from 31 to 15 points (p = 0.002) in the deltoid group. Thus, rPMS applied to mTrPs of neck and shoulder muscles offers a promising approach to alleviate headache frequency and symptom burden. Future clinical trials are needed to examine more profoundly these effects, preferably using a sham-controlled setting.

Altered regional cerebral blood flow and hypothalamic connectivity immediately prior to a migraine headache.

BACKGROUND: There is evidence of altered resting hypothalamic activity patterns and connectivity prior to a migraine, however it remains unknown if these changes are driven by changes in overall hypothalamic activity levels. If they are, it would corroborate the idea that changes in hypothalamic function result in alteration in brainstem pain processing sensitivity, which either triggers a migraine headache itself or allows an external trigger to initiate a migraine headache. We hypothesise that hypothalamic activity increases immediately prior to a migraine headache and this is accompanied by altered functional connectivity to pain processing sites in the brainstem. METHODS: In 34 migraineurs and 26 healthy controls, we collected a series comprising 108 pseudo-continuous arterial spin labelling images and 180 gradient-echo echo planar resting-state functional magnetic resonance volumes to measure resting regional cerebral blood flow and functional connectivity respectively. Images were pre-processed and analysed using custom SPM12 and Matlab software. RESULTS: Our results reflect that immediately prior to a migraine headache, resting regional cerebral blood flow decreases in the lateral hypothalamus. In addition, resting functional connectivity strength decreased between the lateral hypothalamus and important regions of the pain processing pathway, such as the midbrain periaqueductal gray, dorsal pons, rostral ventromedial medulla and cingulate cortex, only during this critical period before a migraine headache. CONCLUSION: These data suggest altered hypothalamic function and connectivity in the period immediately prior to a migraine headache and supports the hypothesis that the hypothalamus is involved in migraine initiation.

Migraine pathways and the identification of novel therapeutic targets.

Introduction: Migraine is a chronic neurovascular disorder characterized by recurrent headache attacks associated with neurological and autonomic symptoms. The pathophysiological mechanisms of the disease are extremely complex, involving hypothalamic and trigeminovascular activation, cortical spreading depression, release of pro-inflammatory peptides, peripheral and central sensitization. The underlying cellular and molecular mechanisms have been scarcely investigated. Recently, genetic studies have suggested that different metabolic pathways could be involved in the pathogenesis of migraine.Areas covered: This review focuses on cellular and molecular mechanisms involved in migraine, suggesting a role for circadian clocks, ion channels, synaptic plasticity, vascular factors, ion metal homeostasis, and impaired glucose metabolism in the pathogenesis of the disease. Accordingly, the article proposes new therapeutic targets that may be of particular relevance for disease prevention.Expert opinion: Several complex molecular mechanisms are involved in setting the genetic threshold for migraine and the pathogenesis of headache attacks. Most promising new therapeutic targets are the modulation of hypothalamic activity and ion channels involved in pain transmission. Further studies in animals and humans are necessary to enhance the elucidation of the molecular mechanisms of migraine and open new avenues for disease prevention.