Migraine and Cluster Headaches

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

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Information Resources / Additional Information and Links to Scientific Studies

  1. In 2013, migraine experts at the University of Mississippi, in the United States, utilized a number of comprehensive health surveys to estimate the incidence of migraine headaches at between 16.2 and 22.7 percent of the population, with a rising incidence, especially in women, where females age 18-44 were experiencing chronic migraine syndromes at the rate of 26.1 percent, and these severe headaches were the third leading cause of emergency room visits. Still, even with the great changes in understanding of the pathology of the migraine syndromes, 80 percent of patients were still treated with the same single type of drug used for decades, the triptan, with sumitriptan, or Imitrex, prescribed in over half of these cases. The implication is that standard medicine needs to expand its treatment perspective greatly, and integrate with Complementary Medicine to prevent headaches and treat comorbid conditions: http://www.ncbi.nlm.nih.gov/pubmed/23470015
  2. In 2015, many headache experts, such as these from the Baylor College of Medicine, in Houston, Texas, USA, note that even for the best experts in the field, that typing the headache to find the best individualized approach to therapy is a big problem. Since migraine symptoms are not specific to primary migraine syndromes, physicians need to spend the time to carefully explore whether the symptoms are due to a headache disorder secondary to other health problems or medication use, and distinguish between episodic migraine status, chronic migraine syndromes, medication overuse syndromes, and neurovascular headaches caused by other health problems: http://www.ncbi.nlm.nih.gov/pubmed/25660280
  3. A relatively new classification of vestibular migraine has been recognized as a significant type that may account for a high percentage of migraine patients with vestibular symptoms of vertigo, head movement intolerance, photophobia and phonophobia, but is still poorly understood. Lab testing and physical exam usually are normal in vestibular headache, and MRI and CAT scans only rule out other vestibular abnormalities. Experts at the University of Pittsburgh School of Medicine point out that until evidence is presented for more radical therapies, treatment options for patients with vestibular headache are largely the same as all other types: http://www.ncbi.nlm.nih.gov/pubmed/23769597
  4. By 2015, increasing use of CT scans and MRI studies to evaluate chronic headache syndromes are being used, but little evidence supporting this expensive and potentially harmful practice exists. The Health Quality Ontario study of 2010 showed in an extensive meta-review of published scientific studies that only 1 prior systematic review, and only 1 small randomized controlled clinical trial, and only 1 observational study was found that met high-quality criteria. Also, these researcher noted that CT scans created accumulative harmful radiation to the sensitive central nervous system tissues, and that MRI studies were less problematic, but could themselves create harmful effects on the brain with prolonged or repeated strong magnetic force. The MRI was safer, and provided better information to fully evaluate soft tissue problems, though. A study of effectiveness for this diagnostic approach was very unclear for outcomes, and a study of whether this diagnostic workup actually alleviated some of the anxiety that contributes to migraine and other headache syndromes showed that there was no measurable benefit in this regard: http://www.ncbi.nlm.nih.gov/pubmed/23074404
  5. A 2013 review of the subject of vestibular migraine syndromes by the esteemed Schlosspark Clinic in Berlin, Germany shows that diagnosis is one of exclusion, with evidence of vestibular symptoms, such as vertigo, with other classic features potentially relevant, such as photophobia and aura. The finding of nystagmus in exam during acute migraine episode, and uncommonly, unilateral vestibular hypofunction as revealed on specialized MRI is relevant, but these can only be tested during the migraine episode to be accurate. The pathophysiology of vestibular migraine appears to linked to the trigeminal nerve system and affects the vestibular system. Lifestyle changes are integrated into care with standard pharmaceuticals by these experts: http://www.ncbi.nlm.nih.gov/pubmed/24057824
  6. A 2015 review of current migraine study by Dr. PJ Goadsby of Minneapolis, Minnesota, U.S.A. notes that less common headache disorders and migraine syndromes, such as hemiplegic migraine, both familial and idiopathic ('sporadic'), migraine with brainstem aura, hypnic headache disorder (waking at night), and the so-called 'exploding head syndrome', are both difficult to diagnose and classify, as well as treat successfully: http://www.ncbi.nlm.nih.gov/pubmed/26252589
  7. A 2015 report from experts at the Darmouth-Hitchcock Medical Center of the Geisel School of Medicine of Dartmouth College, in Hanover, New Hampshire, U.S.A. notes that our current understanding of the migraine syndromes shows that they originate from electrical disturbances in the brain with a spreading cortical depression that involves the brainstem and thalamus, and that this pathology is similar to the current understanding of the epileptic pathophysiology, with some comorbidity seen in the clnic. The migraine syndromes can no longer be limited to just the severe headache episodes, as an array of neurological symptoms occur in these syndromes: http://www.ncbi.nlm.nih.gov/pubmed/25754865
  8. A 2010 randomized controlled study at the China Academy of Chinese Medical Science, in Beijing, China, found that electroacupuncture with alternating 2Hz/100Hz stimulation at the points GB34 and LV3 can effectively suppress cortical spreading depression, a hallmark of migraine pathology, as well as plasma calcitonin gene-related peptide (CGRP) and Substance P (SP) levels, also markers in the migraine pathology: http://www.ncbi.nlm.nih.gov/pubmed/20458901
  9. A 2015 study at the Ludwig-Maximillians University of Munich, in Germany, found in a large cross-sectional study that there was a high correlation between neck and shoulder pain and migraine, with highest association in syndromes with a high frequency of migraines. Such study has been rare, but points to the need to address myofascial syndromes in the holistic treatment protocol: http://www.ncbi.nlm.nih.gov/pubmed/26460336
  10. A 2015 study at Shiraz University of Medical Sciences, in Shiraz, Iran, found that integrating myofascial trigger point therapy with standard medication protocols improved the outcomes considerably: http://www.ncbi.nlm.nih.gov/pubmed/26409701
  11. A large cohort study in China in 2015 showed that, contrary to popular belief, that there was no correlation between elevated blood pressure and any type of headache disorder, including migraines. This multicenter study of nearly 5000 patients, coordinated between experts at Fudan University, Sun Yat-sen University, Central-South University and others in China, and the Norwegian University of Science and Technology, in Trondheim, Norway, should help dispel this misconception that adds unnecessary stress and fear to migraine sufferers concerning blood pressure and fear of stroke: http://www.ncbi.nlm.nih.gov/pubmed/26438330
  12. A 2003 study published in the Oxford Journals shows how Sildenafil (Viagra and Revatio) may induce a migraine syndrome over time by repeatedly stimulating cGMP (cyclic guanosine monophosphate) vasodilation via inhibition of phosphodiesterase-5. A randomized controlled human study showed that 10 of 12 migraine sufferers had symptoms induced by Viagra independent of the effects on blood pressure, heart rate, and temporal and radial artery diameter. The repeated effects of cGMP alterations could also contribute to onset of the migraine syndromes: http://brain.oxfordjournals.org/content/126/1/241
  13. A 2010 study by experts at Brigham and Women's Hospital, in Boston, Massachusetts, U.S.A. shows that evidence that confirms a risk of migraine syndrome onset with oral contraceptive use: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938905/
  14. A 2015 meta-review or scientific studies of the use of Gabapentin (Neurontin) in the treatment of headache disorders, now commonly prescribed off-label, by experts at the Boston University School of Medicine and the Perelman School of Medicine at the University of Pennsylvania, in the United States, showed that this drug did not show sufficient evidence to be used a a primary therapy for migraine disorder, and that modest benefits were seen for other headache disorders, but that only 7 human clinical trials of Class 2 or higher grade were found that showed modest statistical benefit. The adverse or side effects of Gabapentin are often alarming: http://www.ncbi.nlm.nih.gov/pubmed/26398728
  15. A 2015 randomized controlled study at the Beijing University of Chinese Medicine used functional MRI studies to show that functional connectivity (FC) was reduced in cortical vestibular areas of the brain, such as the right frontoparietal network (RFPN) in migraine patients without aura, and that this was reversed with acupuncture treatment. The acupuncture treatments involved 5 treatments per week for 4 weeks, using an individualized selection of points from a set approved by Chinese guidelines and the WHO list of standard acupuncture points used to treat migraine, and performed by clinicians with at least 7 years of experience. Such study design finally reverses the long history of using study design to achieve failure with acupuncture, now widely acknowledged. The set of points used include SJ23, GB8, GB20, Taiyang, SJ5, LV3, LI4, GB34, and GB41. Such study also shows that standard treatment in the U.S., with needle stimulation only performed once per week or less is inadequate: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411327/
  16. A 2012 report from the University of Padova and CNR Institute of Neuroscience, in Italy, describes the current findings of migraine and cluster headache pathophysiology, emphasizing the contribution of a variety of systems in the complex neurovascular mechanism. To treat this variety of systems, a more holistic approach is needed: http://www.ncbi.nlm.nih.gov/pubmed/23190076
  17. A 2015 study at the Leiden University School of Medicine, in The Netherlands, noted that use of mass spectrometry imaging has revealed the complex phenomena of cortical spreading depression hat occurs in migraine pathology, especially subjects with a familial propensity. These studies reveal that a number of biochemical metabolites and protein peptides are involved, and that functional changes occur in the brain cortex as well as the thalamus. Such study demonstrates the need for a more comprehensive and holistic approach in treatment, as well as the lack of real understanding of the pathology in standard medicine for many decades:http://www.ncbi.nlm.nih.gov/pubmed/25877011
  18. A 2013 study of acupuncture in the treatment protocol for chronic migraine patients, conducted by the University of Padua, Italy, Department of Neurosciences, found that a course of simple acupuncture administered twice a week for 10 weeks produced significantly better results at 6 months in measures of pain intensity and pain-related symptoms, as well as a significant reduction in the need for triptan drugs to treat acute migraine episodes, compared to chronic use of a valproic acid medication such as Depakote. The outcome measures were of course better with the pharmaceutical drug at 1 month out, but significantly better at 6 months and 1 year with the short acupuncture course, and the reports of adverse health effects with the valproic acid medication came from nearly half of the study participants taking the medication, while there was absolutely no reports of adverse health effects from the acupuncture. Such study clearly demonstrates that acupuncture as a Complementary Medicine could also significantly reduce the risk of a rebound headache syndrome, a big concern in medicine today: http://www.ncbi.nlm.nih.gov/pubmed/23511357
  19. A 2013 large, multi-center, randomized controlled human clinical trial comparing long-term benefits of acupuncture therapy versus use of Topiramate for migraine treatment, at 5 University Medical Schools in Taiwan, found that acupuncture therapy resulted in significantly fewer moderate to severe headache episodes per month compared to the individual baseline occurrence rate, than utilization of Topiramate. This study also found that the specific acupuncture treatment utilized worked better for patients reporting a throbbing quality of the pain. Consecutive patients entering these migraine clinics, that agreed to the study, were randomly assigned to either the acupuncture or topiramate treatment. Of course, some patients may choose to combine these therapies to try to gain a greater outcome success: http://www.ncbi.nlm.nih.gov/pubmed/23370087
  20. A 2015 meta-analysis of all published randomized controlled human clinical trials (RCTs) of acupuncture in the treatment of migraine headache syndromes, by the Fujan University of Traditional Chinese Medicine, in China, found that significant evidence proves that real, or verum acupuncture treatment outperforms so-called placebo or sham acupuncture controls by a good margin, dispelling the often repeated view that acupuncture works in the treatment by placebo effect only: http://www.ncbi.nlm.nih.gov/pubmed/26718001
  21. A 2015 meta-review and clinical assessment of integration of acupuncture into migraine treatment protocol, by the Michigan Head Pain and Neurological Institute (MNNI), in Ann Arbor, Michigan, noted that acupuncture seems to be at least as effective as conventional drug therapy for prevention of future migraines, and presents a completely safe, cost-effective and long-lasting effect, and is part of a more complex holistic treatment protocol in clinical practice that could also prompt sensible lifestyle changes. The MHNI is a world-renowned specialty and research center that is the only one of its kind to earn national accredidation: http://www.ncbi.nlm.nih.gov/pubmed/25683754
  22. A 2014 randomized controlled study with functional MRI of the brain, involving more than 80 patients with chronic severe migraine syndromes, at Chengdu University of Traditional Chinese Medicine, in Chengdu, China, found that long-term effects of an 8-week course of acupuncture produced a significant improvement in regional homogeneity in key areas of the brain, such as the cingulate gyrus and insula, correlating with decreased pain: http://www.ncbi.nlm.nih.gov/pubmed/24915066
  23. A 2015 meta-review of comparative effectiveness of the variety of proven treatments for migraine and cluster headache syndrome was begun at Chengdu University of Traditional Chinese Medicine and The Third Clinical College of Zhejiang Chinese Medical University, in Huangzhou, China, to assemble for the first time the wide array of evidence for patients and physicians in a systematic and individualized manner. Evidence now supports a wide array of pharmacological and non-pharmacological therapies, of both direct and indirect effects, and these experts hope to provide an evidence-based guideline for integrative care:http://www.ncbi.nlm.nih.gov/pubmed/25948410
  24. A 2012 report from the Kitasato University School of Medicine, Department of Neurology, in Japan, outlines the current approach to most chronic frequent migraine syndromes, defining many as a complex spreading cortical depression or a refractory syndrome (medication rebound effects). The increased protocol of tapering of common migraine medications such as triptans and NSAIDS, and then instituting of a more holistic preventive medicine protocol is utilized, and evidence-based: http://www.ncbi.nlm.nih.gov/pubmed/23196488
  25. A 2014 review of guidelines for migraine and cluster headache syndromes, a the Neurological Institute of the Ohta-Atami Hospital, in Japan, recommended that we move along in adopting the 3rd Edition of the International Classification of Headache Disorders, acknowledging that it is usually difficult to distinguish between chronic migraine and medication overuse headaches, and so physicians should often diagnose patients with both or these classifications, thus better addressing treatment needs. This institute also noted that a number of key contributing underlying risk factors need to be addressed in a more holistic approach to both diagnosis and treatment, and that the past one-size-fits-all approach to the treatment of migraines be changed: http://www.ncbi.nlm.nih.gov/pubmed/25672691
  26. A 2012 study at Keio University, Department of Neurology, in Japan, reported that acupuncture is considered a proven treatment for headache syndromes, and that laboratory studies at this university demonstrated that acupuncture stimulation appears to affect the threshold reduction of cortical spreading CNS depression triggered in the trigeminal nerve pathway, a proven hallmark of the pathogenesis of migraine syndromes: http://www.ncbi.nlm.nih.gov/pubmed/23196597
  27. A 2012 study at the Headache Center Berlin at the Sankt Gertrauden Krankenhaus Hosptial, showed that there was a measurable difference between the positive effects of so-called placebo acupuncture and so-called real acupuncture stimulation in study. Many past studies noted significant benefits of acupuncture treatment for migraines, but noted that the points chosen as a placebo stimulation also produced a significant benefit, and so summarized that the real acupuncture did not outperform the so-called placebo acupuncture enough to prove effectiveness. In this study, a transcranial Doppler ultrasound was used to show that the real acupuncture stimulation not only decreased pain intensity and frequency of migraine, but that cerebrovascular spasm, or vasotonus, was also significantly reduced in the group receiving real acupuncture, but not in the group receiving the so-called placebo or sham acupuncture stimulation. This would indicate that real acupuncture stimulation could reduce the hypersensitivity of vascular response to autonomic stimuli in the migraine syndrome: http://www.ncbi.nlm.nih.gov/pubmed/22888768
  28. A 2014 study with functional MRI at Chengdu University and Xidian University, in China, and the German Cancer Consortium, in Heidelburg, Germany, showed that different effects were seen from stimulation of active and inactive acupuncture points, with active trigger points showing potential effects that could regulate key areas of the brain and brainstem, as well as restore functional homeostasis to key pain centers. Active acupuncture points are commonly noted by observing momentary sensations by the patient, or by the physician noting either sensation at the needle handle or local twitch response, which is traditionally called de qi, and some mechanical means of measurement are sometimes used with electrical resistance measured at the points. Such study demonstrates that the common belief in the United States that acupuncture stimulation should elicit no sensation, such as momentary pain or discomfort, has been a misguided belief that has decreased the effectiveness. Once acupuncture points are activated, or de qi obtained, electrical stimulation may also be used to enhance these homeostatic effects: http://www.ncbi.nlm.nih.gov/pubmed/24915066
  29. A 2012 randomized controlled study at Chengdu University Medical College of TCM, in Chengdu, China, showed that a simple traditional set of acupuncture points used to treat migraine headaches, SJ5, GB34, GB20, outperformed both a control set of points, ST8, LI6, and ST36 (also commonly used to treat headache), and a group of migraine patients that received no additional therapy to their normal treatment course. This study also utilized both PET scan and CT to evaluate effects in the brain, noting that the traditional acupuncture chosen showed significantly more stimulation in key centers of the brain associated with migraines, the insula, post-cingulate gyrus, precuneus, and middle cingulate cortex, as well as key areas of the middle and frontal cortex, while decreasing excess activity in key areas associated with migraine pathology, including the hippocampus, fusiform gyrus, and postcentral gyrus, showing that acupuncture stimulation specific to migraine therapy actually is proven to beneficially modulate the brain activity to correct the mechanisms of the disease: http://www.ncbi.nlm.nih.gov/pubmed/22894176
  30. A 2014 multicenter study at Nanjing University, Chengdu University, Zhejiang Medical University, and the National Center of Biochemical Analysis, in China, found that acupuncture and electroacupuncture also helped relieve the Migraine Syndrome by restoring the abnormal metabolic profile and glutamate toxicity syndrome associated with the disease: http://www.ncbi.nlm.nih.gov/pubmed/24592282
  31. By 2015, we see that standard medicine has recognized the failures of pharmacological treatment of the migraine syndromes and is developing new technologies for treatment. One of these approaches, the use of implanted neurostimulation is showing promise. Electroacupuncture stimulation has proven to have similar effects without the risks, high costs, and potential adverse effects, and could be tried first in a sensible world concerned with risk versus benefit: http://www.ncbi.nlm.nih.gov/pubmed/25688595
  32. A 2014 multicenter study at the University of Eastern Finland, and the Sechenov Institute of Saint Petersburg, Russia, confirmed that glutamate toxicity, inducing unhealthy changes at the NMDA glutamate receptors in the brain, along with the mGluR5 receptors, induced higher intracellular calcium ion levels and homocysteine-activated sensitization in the migraine syndrome. Such study shows how many foods trigger migraines, as glutamates are created in the food industry to create increased desire and addiction to processed foods: http://www.ncbi.nlm.nih.gov/pubmed/24266734
  33. A 2012 article in the Canadian Journal of Neurological Science outlines current guidelines for migraine care and prevention (prophylaxis) by the Canadian Headache Society, which includes a number of herbal medicines strongly evidenced, including Butterburr (Petasites) and Feverfew (Tenacitum parthenium), as well as the combination of CoQ10, B2 riboflavin and magnesium supplement: http://www.ncbi.nlm.nih.gov/pubmed/22683887
  34. A 2008 article from a migraine specialist published in Nature, Nature Reviews Neurology, confirms that standard medical protocol for migraine treatment includes Complementary medicine and non-pharmacological treatments (meaning herbs and nutrient supplements): http://www.nature.com/nrneurol/journal/v4/n9/full/ncpneuro0861.html
  35. A 2010 article in the medical journal Neurological Science by the Women's Headache Center of the University of Turin, Italy, showed that meta-reviews of acupuncture by the Cochrane review found acupuncture effective for the treatment and prevention of migraine, as well as riboflavin, CoQ10, ALA, Butterburr, and Feverfew, and that magnesium supplement was particularly effective for children and sufferers of menstrual migraine. The research review found that the herbal extract of Feverfew shows considerable variation of the active chemicals in herbal products, explaining the variance in outcomes in clinical trials. These remedies should be combined to achieve an effective and comprehensive integrated treatment protocol, as no single pharmaceutical, herbal or nutrient medicine is expected to reduce migraine frequency enough on its own: http://www.ncbi.nlm.nih.gov/pubmed/20464605
  36. A 2013 clinical study of the use of Vitex agnus-castus in the treatment of menstrual migraine, by the Headache Clinic of the Institute of Neurology Mediterranean Neuromedicine, in Pozzilli, Italy, concluded that Vitex in clinical use appeared to improve the frequency and intensity of the menstrual migraines, and is very safe and beneficial. The Institute called for further randomized controlled studies to confirm the effects: http://www.ncbi.nlm.nih.gov/pubmed/22791378
  37. A 2009 article published in the medical journal Clinical Journal of Pain by the New York Headache Center stated that most migraine patients did not receive significant relief with pharmaceutical medications, even with the wide array of medications now used, and that a detailed meta-review of scientific study shows that subsets of patients are sensitive to glutamates (food additives to stimulate addiction), nitrites (preservatives), nitrates (a chemical in aged foods and wine), caffeine, alcohol, tyramine (aged or smoked meats, chesees, chocolate, alcoholic beverages, and soy condiments), and phyenylethylamine (chocolate) as potential triggers. The use of a food diary to correlate triggers methodically is highly recommended, as is the use of a combination of magnesium, Petasides hybridus (butterburr), feverfew, CoQ10, riboflavin, and ALA (alph-lipoic acid). These protocols should be combined with acupuncture, herbal medicine, physiotherapy and pharmacological medicines to achieve the best integrative and Complementary protocol: http://www.ncbi.nlm.nih.gov/pubmed/19454881
  38. A 2005 article published in Australian Family Physician reveals that current migraine protocol includes evidence-based acupuncture and nutritional supplements, instruction in dietary and environmental factors, and a mind-body approach, pioneered by Traditional Chinese Medicine in the standard treatment approach: http://www.ncbi.nlm.nih.gov/pubmed/16113701
  39. A research abstract that demonstrates the complexity and holistic nature of the migraine and cluster headache mechanisms in pathophysiology published in Pharmacology and Toxicology Journal in 2001http://www.ncbi.nlm.nih.gov/pubmed/11555322 If you have trouble accessing this database by clicking on this address, Google PubMed or NCBI.
  40. Another research abstract that demonstrates the complexity and holistic nature of the migraine and cluster headache mechanisms in pathophysiology published in the journal Cephalalgia in 2001http://www.ncbi.nlm.nih.gov/pubmed/11595008 If you have trouble accessing this database by clicking on this address, Google PubMed or NCBI, and search for 11595008.
  41. The U.S. government maintains a research database website for the public that can be quickly found at http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed&itool=toolbar If you have trouble accessing this database by clicking on this address, Google PubMed or NCBI.
  42. A 2005 randomized controlled human trial of Coenzyme Q10 and Vitamin B2 riboflavin at the Headache and Pain Unit of Unversity Hospital Zurich, Switzerland, found that this protocol produced a dramatic success rate over placebo over a 3 month period: http://www.ncbi.nlm.nih.gov/pubmed/15728298
  43. A 2009 assessment of standard therapy for migraines, published in the Journal of Headache Pain, summarizes that almost no pharmaceutical medicines have been developed for migraine therapy, but various pharmaceuticals intended to treat other disorders have been used in the past. Recently, specific therapies have been found, one revisiting the delivery of the old ergot chemicals derived from herbal medicine, but these are as yet unproven. Some proof of efficacy has been found for herbal medicine, though, as well as standard pain killers. http://www.ncbi.nlm.nih.gov/pubmed/19795182 If you have trouble accessing this database by clicking on this address, Google PubMed or NCBI.
  44. Research in 2009 demonstrates with sound clinical study that over 40% of patients with classic migraine with aura (prodrome) found significant benefit from gingko biloba extract if they persisted with therapy for 2 months. Of course, quality professional extract from a professional concerned with quality is important with almost no regulation of the herbal industryhttp://www.ncbi.nlm.nih.gov/pubmed/19415441
  45. Research in 2008 reveals how herbs like Feverfew (Tancetum parthenium) are proven to exert effects of genetic stimulation of key inflammatory mediators, and that this may reveal the physiological mechanisms which account for its success in migraine therapy: http://www.ncbi.nlm.nih.gov/pubmed/18066113
  46. Research in 2012 in Florence Italy, published in the European Journal of Pain, revealed that St. John's Wort, or Hypericum perforatum, both treated and prevented migraine pain, affecting pain hypersensitivity, making this herbal extract a valuable part of the overall protocol: http://www.ncbi.nlm.nih.gov/pubmed/23152076
  47. A meta-review by China Academy of Chinese Medical Sciences showed that the most widely used herbal patent medicine for migraines in China, Tianshu Capsule, a combination of the classic migraine formulas Da Chuan Xiong Fang and Tianma Gouteng Yin, is effective, and provides a variety of direct and indirect effects to both reduce migraine symptoms and restore homeostasis in key areas of the brain: http://www.hindawi.com/journals/ecam/2014/580745/
  48. A 2013 meta-review of studies of Tianshu Capsule in the treatment of migraine syndromes, by Liaoning University of Traditional Chinese Medicine, found that evidence supports the use of this common herbal formula combination, especially as an integrative protocol, with fewer adverse side effects from the total treatment protocol: http://www.ncbi.nlm.nih.gov/pubmed/23596805
  49. Research in 2006 in China shows the extent of new herbal products proven to effect migraines: a novel approach is to use a small dose of herbs as a nose drop to stop the vasoreactivity in migraines: http://www.ncbi.nlm.nih.gov/pubmed/16800989 If you have trouble accessing this database by clicking on this address, Google PubMed or NCBI.
  50. Research in 2002 at the Jefferson Headache Center at Thomas Jefferson University in Philadelphia produced the first human trial results confirming the efficacy of Coenzyme Q10 for migraine treatment: http://www.ncbi.nlm.nih.gov/pubmed/11972582.
  51. Continuing research of CoQ10 at the Institute of Biochemistry at Polytechnic University of Marche, in Ancona, Italy, confirmed the beneficial effects of CoQ10 for many disorders, including neurological and vascular: http://www.ncbi.nlm.nih.gov/pubmed/16205466.
  52. By 2004, a review of various human clinical trials revealed the potential for a combination of CoQ10, B12, B2 and magnesium in the overall integrative protocol to treat migraine: http://www.ncbi.nlm.nih.gov/pubmed/15196887.
  53. The role of magnesium in the migraine pathology has been well known for some time. In 1998, the New York Headache Center published an article in Clinical Neuroscience outlining the complexity of the mechanism by which dysfunction of the magnesium metabolism may affect the migraine pathophysiology, with effects on the serotonin and glutamate NMDA receptors, as well as other neurotransmitter receptors, as well as nitric oxide synthesis and release (vasodilation control): http://www.ncbi.nlm.nih.gov/pubmed/9523054
  54. By 2009, the New York Headache Center published an article reviewing research on magnesium depletion during migraine episodes, and stated that this effect alters neurotransmitter release, leads to hyperaggregation (accumulation) of platelets, and promotes a spreading of depressed function in the cortex: http://www.ncbi.nlm.nih.gov/pubmed/19271946
  55. In 2007, experts at Harvard Medical School proposed that migraine pathophysiology may begin with a series of membrane destabilizing effects that involve not only magnesium, but other mineral ions involved in membrane channels and electrochemical controls, such as potassium, calcium and sodium, leading to a generalized dysfunction called cortical spreading depression: http://www.ncbi.nlm.nih.gov/pubmed/17925161
  56. In 2004, experts at the University Pierre and Marie Curie, in Paris, France, published research that showed that simple oral magnesium supplementation may not be enough to correct the dysfunction in magnesium metabolism in the brain of migraine sufferers. These researchers postulated that hypofunction of the biological clock (diurnal neuroendocrine regulation) is integral to this magnesium ion dysfunction, and proposed use of not only magnesium supplement, but melatonin, L-tryptophan (or 5HTP), and taurine, as well as darkness therapy, where the patient spends time in a completely darkened room with eye covering to stimulate increased melatonin metabolism: http://www.jle.com/e-docs/00/04/08/99/article.md
  57. A 2009 review of oral contraception use for migraine sufferers finds that the use of combined oral contraceptives is always contraindicated for patients suffering migraine with aura. Hormone-induced headache and estrogen withdrawal headache are also accepted as definitive diagnoses by the International Classification of Headache Disorders: http://wwww.ingentaconnect.com/content/ftd/ern/2009/00000009/00000003/art00012.