A Solution For The Chronic Migraine Problem

Migraine headache is an episodic headache disorder. Over 3.2 million Canadian adults and an estimated 200,000 to 300,000 children in this country suffer from the pain and debilitating effects of migraine headaches. Considered a genetically inherited disorder, the condition most often hits people 20 to 50 years old. Women are twice as likely as men to suffer migraines. One study from the Migraine Association of Canada reported 77% of migraine sufferers cancel family and social activities when having an attack, 19% reported absences from work. Based on the 5.4 million workdays lost annually to migraine, this is estimated to cost the Canadian economy around 500 million dollars a year. This condition is under-treated and under-diagnosed worldwide. Not all headache sufferers seek medical attention, but those who do, generally consult family practitioners, internists or pediatricians, ophthalmologists, and neurologists 

In practice there are, broadly speaking, two types of migraine. The most common is called migraine without aura (common migraine) and this accounts for 85% of all sufferers. These are episodes of severe pain that may affect only one side of the head, although sometimes may be bilateral. It is usually, but not always, associated with feeling sick in the stomach or being sensitive to light, sound or movement of the body. Typically, the sufferer would wish to lie down in a dark and quiet room and wait for the storm to pass. The second most common type is called migraine with aura (classical migraine). The aura is a disturbance in the nervous system involving the vision, with bright flashing lights, black spots or partial loss of vision. These disturbances are usually short-lived, being less than one hour for most sufferers, and almost invariably pass away leaving no long-lasting effects 
Trigger factors including stress, dental problems, weather changes, cheese, chocolate, wine and beer sensitivity, gastrointestinal inflammation, female sex hormones fluctuations, minor head trauma or whiplash neck injury, eating disorder, high levels of blood lipids and free fatty acids (arachidonic acid) are underlying factors in development of migraine.

Advances in our understanding of the mechanisms of migraine have facilitated rational treatment of the condition. Migraine prone patients are those who have hereditary abnormality of the brain oxidative system and magnesium deficiency that makes the brain nerve cells vulnerable to the trigger factors. The latter also stimulate platelet aggregation and release of a substance called serotonin that causes constriction of the brain blood vessels and secondary focal neurologic symptoms and aura. Following the aura there is dilatation of the extracranial blood vessels that causes the headache phase. The accumulation of certain chemicals (e.g. bradykinin) around the cerebral blood vessels, causes periarterial sterile inflammatory response that leads to the pain characteristic of migraine. As the immune response in migraine prone patients is altered, the migration of Opioid-containing immune cells, which constitute the brain pain controlling system, to the inflamed sites is delayed which causes an increase of the migraine pain.

Any sufferer of migraine, assuming they want treatment, has basic choice between non-drug and drug treatments. The many side effects of pharmacological treatment and prophylaxis derived the attention of the scientists of PhytoMe Natural Specialty Products company towards the natural products that could be of help to migraine patients. 

The most exciting news is that PhytoMe introduced a non-pharmacological, completely natural product in the form of Balm (MigraCell). Once this Balm is applied to the site of pain and to the nasal mucosa, it penetrates the skin, nasal mucosa and the fine capillary wall to the circulation to exert fast abortive effect in migraine. As most of migraine patients suffer gastrointestinal upset, they don't benefit from any orally administered drug therapy. Thus, the design of MigraCell Balm local application insures the maximum benefit of migraine patients. The MigraCell Balm can also exert prophylactic effect if applied to the nasal mucosa twice daily in attack free time. 

Migraine and its accompanying symptoms, complications, warning signs and mechanisms have been extensively studied before designing MigraCell Balm. Literatures including experimental, clinical studies and scientific facts about the herbal ingredients of this remedy have been studied very carefully. All the ingredients act synergistically without side effects. Each of the ingredients acts by reversing one or more of the mechanisms that cause migraine. MigraCell Balm regulates the altered immune response and activates the brain Opiate system to control the pain. It also inhibits platelet aggregation and the release of serotonin and histamine to relieve the vasospasm and improve the brain circulation. It inhibits arachidonic acid, a fatty acid, which stimulates the inflammatory reaction around the neurovascular system of the brain. MigraCell Balm improves the mitochondrial oxidative metabolisms, inhibits the neuronal hyperexcitation, and increases tolerance to focal hypoxia. it stops cellular deterioration due to hypoxia and reoxygenation and leads to a significantly greater recovery of cellular function following the hypoxic insult. Finally, it exhibits sedative and anxiolytic action. 

The main active herbal ingredients in MigraCell Balm are Feverfew, Melissa officinalis, Chamomile, Leguminosae, Linden). The non- herbal active ingredients include Salmon Calcitonin, Magnesium, taurine and riboflavin. All the ingredients used has been proved to be safe, non-toxic and without any side effects through careful Monograph study of each of them.

PhytoMe Natural Specialty products company also formulated the nutritional supplementation in the form of capsules that contain the daily requirement of all nutritional elements essential for migraine prophylaxes. Although many drugs have value for migraine prophylaxis, this nutritional measure, suggested here, might have particular merit owing to the versatility of their actions, their safety and lack of side effects and their long-term favorable impact on vascular health. This nutritional supplementation is rich in Omega 3 of marine source (fish oil) that has been proved by clinical study to be a very effective agent for prophylaxis against migraine through different pathways. It has platelet-stabilizing action as it reduces platelet aggregation with secondary reduction in the serotonin level in the blood and inhibition of the cerebral vasospasm. Omega 3 increases the natural antibodies against bradykinin and increases the level of antioxidants in the blood that leads to inhibition of arachidonic acid (AA). Both actions of Omega-3 reduce the sterile inflammatory response around the neurovascular system of the brain and inhibit the pain of migraine. It also inhibits any allergic reactions in patients with migraine secondary to food hypersensitivity. Omega-3 is a crucial component of synaptic cell membranes and so it alleviates the spreading cortical depression, which could cause migraine. The anti-thrombin III (a blood anti-clotting factor) activity of Omega-3 reduces the possibility of the occurrence of stroke which could happen as a complication of sever migraine. As dietary supplementation with Omega-3 fatty acids has a beneficial effect on symptoms of dysmenorrhea in adolescents, it constitutes a very effective prophylactic agent in cases of migraine in which the dysmonorrhea is the main trigger factor. The nutritional capsules are also a rich source of magnesium and vitamins, which have been proved by clinical trial to be very important in migraine prophylaxis. 

PhytoMe Natural Product scientists believe that it is the right of the patient, to know a brief account of important information about the remedy they use, as well as the sources of such information. The following information about the different active ingredient in migraine remedy has been confirmed by experimental and clinical studies.

Feverfew, Tanacetum Parthenium Compositae: it has inhibitory effect on inflammation, blood platelet aggregation, secretion of serotonin and histamine and the contractile responses of the smooth vascular muscles. These effects could explain the ability of Feverfew extract to reverse the cerebral vasospasm that occurs in migraine attacks and sometimes leads to cerebral ischemia. Studies also showed that the mean frequency of genetic chromosomal abnormalities in the Feverfew user group was lower than that in the non-user group. Although this difference was not significant due to the small number of patients, this observation merit further studies to see whether the Feverfew has any effect on the chromosomal abnormalities found in many migraine patients. Systematic review was made to look at the evidence for or against the clinical effectiveness of Feverfew in migraine prevention. Two independent reviewers read all articles. Five trials met the inclusion/exclusion criteria. The majority favor Feverfew over placebo.

Balm Melissa Officinalis: It inhibits the inflammatory processes, exhibits high analgesic and anxiolytic activity. It has been also found that it contains high concentrations of total ascorbic acid, which modulates the secretion of immunoreactive beta-endorphin (brain opiate system for controlling the pain)

Chamomile: It has antihistaminic effect as well as a profound anti-inflammatory activity. 

Leguminosae: it inhibits platelet aggregation and protects the cerebral vessels against vasospasm and blood clot occlusion 

Linden, Tiliaceae: It has anti-histaminic, sedatives, tranquilizer and anxiolytic effect.
 
Salmon Calcitonin: It has analgesic effect through the secretion of immunoreactive beta-endorphin, or controlling the pain.

Magnesium: The available evidence suggests that up to 50% of patients during an acute migraine attack have lowered levels of ionized magnesium. Infusion of magnesium results in rapid and sustained relief of an acute migraine in such patients.

Taurine: It reduces cellular deterioration due to hypoxia and reoxygenation and helps recovery of cellular function following the hypoxic insult. 

Riboflavin: It regulates the altered mitochondrial oxidative metabolism, which may play a role in migraine pathogenesis. It also helps keeping healthy immune system.

Vitamin B6 (Pyridoxal Phosphate): As supportive treatment, a vitamin B6 (pyridoxal phosphate) substitution appears useful in histamine-intolerant patients. It seems to be crucial for diamine oxidase activity, (an enzyme essential for histamine degradation and which is deficient in those patients). 

References
(1) Sumner H. Salan U. Knight D W. Hoult J R S. Inhibition Of five Lipoxegenase and Cyclooxygenase in leukocyte by Feverfew Involvement of Sesquiterpene Lactones and Other Components. Biochemical Pharmacology 43 (11). 1992. 2313-2320. 

(2) Hewlett MJ. Begley MJ. Groenewegen WA. Heptinstall S. Knight DW. May J. Salan U. Toplis D. Sesquiterpene Lactones from Feverfew, Tanacetum Parthenium- Isolation, Structural Revision, activity against Human Blood Platelet Function and Implications for Migraine Therapy. Journal of the Chemical Society. Perkin Transactions 1. (16): 1979-1986, 1996 Aug 21.

(3) Barbs, R. W. J. Salon, U. Knight, D. W. Hoult, J. R. S. Feverfew and vascular smooth muscle: extracts from fresh and dried plants show opposing pharmacological profiles, dependent upon sesquiterpene lactone content. Planta Medica. 1993. 59: 1, 20-25.

(4)Anderson D. Jenkinson PC. Dewdney RS. Blowers SD. Johnson ES. Kadam NP. Chromosomal aberrations and sister chromatid exchanges in lymphocytes and urine mutagenicity of migraine patients: a comparison of chronic Feverfew users and matched non-users. Human Toxicology. 7(2): 145-52, 1988 Mar.

(5)Vogler BK. Pittler MH. Ernst E. Feverfew as a preventive treatment for migraine: a systematic review Cephalalgia. 18(10): 704-708, 1998 Dec.

(6)Palevitch D. Earon G. Carasso R. Feverfew (Tanacetum Parthenium) as a prophylactic treatment for migraine- A Double-blind Placebo-Control study Phytotherapy Research. 11(7): 508-511, 1997 Nov.

(7) Yang Z. Copolov DL. Lim AT. Ascorbic acid augments the adenylyl cyclase-cAMP system mediated POMC mRNA expression and beta-endorphin secretion from hypothalamic neurons in culture. Brain Research. 706(2):243-8, 1996 Jan 15).

(8)Grimble R F. Effect of antioxidative vitamins on immune function with clinical applications. International Journal for Vitamin & Nutrition Research 67(5). 1997. 312-320. 

(9) Soulimani, R. Younos, C. Fleurentin, J. Mortier, F. Misslin, R. Derrieux, G. Study of the biological activity of Melissa officinalis on the mouse central nervous system in vivo and on rat duodenum in vitro. [French] Plantes Medicinales et Phytotherapie. 1993. 26: 2, 77-85.

(10)Miller, T. Wittstock, U. Lindequist, U. Teuscher, E. Effects of some components of the essential oil of chamomile, Chamomilla recutita, on histamine release from rat mast cells. Planta Medica. 1996. 62: 1, 60-61. 

(11) Loggia, R. della. Carle, R. Sosa, S. Tubaro, A. Evaluation of the anti-inflammatory activity of chamomile [Chamomilla recutita] preparations. Planta Medica. 1990. 56: 6, 657-658. 

(12) Ustdal M. Dogan P. Soyuer A. Terzi S. Treatment of migraine with salmon calcitonin: effects on plasma beta-endorphin, ACTH and cortisol levels. Biomedicine & Pharmacotherapy. 43(9):687-91, 1989).

(13) (Mauskop A. Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clinical Neuroscience. 5(1):24-7, 1998).

(14) Michalk D V. Wingenfeld P. Licht C. Protection against cell damage due to hypoxia and reoxygenation: The role of taurine and the involved mechanisms. Amino Acids (Vienna) 13(3-4). 1997. 337-346.

(15)Schoenen J. Jacquy J. Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis: A randomized controlled trial. Neurology 50(2). 1998. 466-470.

(16)Cukier C. Waitzberg D L. Biological activity of fish oil. [Portuguese] Arquivos de Gastroenterologia 33(3). 1996. 173-178).

(17)Harel Z. Biro F M. Kottenhahn R K. Rosenthal S L. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. American Journal of Obstetrics & Gynecology 174(4). 1996. 1335-1338).

(18)Mori T A. Beilin L J. Burke V. Morris J. Ritchie J. Interactions between dietary fat, fish, and fish oils and their effects on platelet function .Thrombosis & Vascular Biology 17(2). 1997. 279-286.

About the Author:

Dr. ESTHER SHEHATA
Head of Research and Development in Dermamed Pharmaceutical company. Working on extraction and 
purification of the useful active ingredient from different types of herbs proved to be of great medical help
in treating arthritis, severe eczema and other skin diseases. 

Degrees:
Ph.D. in Clinical Science.
M.Sc in Medicine, and Clinical Science.
M.D

Experience:
Involved in different Medical fields:
Working as a Physician, doing complete patients medical examination and attending clinical meetings.
As a Pathologist doing all the advanced techniques in Hematology, Bone marrow puncture and examination, 
Biochemistry, Microbiology and Immunology. 

Involved in UBC Research:
As a Post Doctorate fellow in UBC Lung Pathology department performing lung culture and 
Histoimmunocytochemical techniques. Working on different projects in lipid research doing purification
techniques using the HPLC system. Preparing antibodies in rabbits and doing Eliza test as aquality control .
Extracting the DNA from human blood and doing the PCR technique as a quality control.
Performed different surgical procedures and trials on animal models.

Involved in UBC Research:
As a Post Doctorate fellow in UBC Lung Pathology department performing lung culture and
Histoimmunocytochemical techniques.Working on different projects in lipid research doing purification
techniques using the HPLC system. Preparing antibodies in rabbits and doing Eliza test as aquality control .
Extracting the DNA from human blood and doing the PCR technique as a quality control.
Performed different surgical procedures and trials on animal models.

Publications:
Cytodynamics of in Vitro Developing Airways and Interaction with Extracellular Matrix Proteins, Lung (1996) 174: 359-371.

Two Different Patterns of Airway Branching Regulated by Different Components of the Extracellular Matrix in Vitro. Experimental Lung Research, 22:593-611, 1996.

Immune Deficiency in Hodgkin and Non-Hodgikin Lymphoma Biomedicine Journal, 1980, 32, 128-133.