Migraine headache is an episodic headache disorder. The treatment of migraine has not only medical but also serious economic and social implications. Both the avoidance of migraine trigger factors and the use of non-pharmacological therapies have a part to play in overall migraine management.
SYMPTOMS COMPLEXES IN MIGRAINE:
The aura may last 20 to 30 minutes and may include one or more of the following:
Mood changes (commonly a sense of elation associated with hyperactivity)
Increased appetite (particularly for sweet foods).
Blindspots, It clears as the headache appears.
Sensory hyperacuity: light may be perceived as dazzling or may provoke pain, sounds may appear unnaturally loud, and smells may be more intense during (or even before) the headache phase.
Focal Neurological Symptoms
These neurological symptoms may arise from the cerebral cortex, brain stem, or cerebellum due to diminished cerebral blood flow to the corresponding part of the brain
It is unilateral in two thirds of patients. It commonly starts as a dull ache in one temple and then spreads over that side of the head or the whole head or may remain localized. The pain is usually constant and assumes a pulsatile or throbbing quality when sever. It may consistently affect the same side of the head or may move from side to side, even in the one migraine episode. Pain may radiate down the neck to the shoulder or, in some cases, to the arms and even the leg on the same side of the body.
Nausea sometimes precedes the onset of headache but commonly evolves as the attack progresses and may culminate in vomiting. Diarrhea is associated in about 20%of patients.
PAIN-SENSITIVE CRANIAL STRUCTURE
The foundation for any study of the causes and treatments of headache is knowledge of the pain-sensitive structures and pain-conducting pathways within the cranium.
THE ORIGIN OF MIGRAINE HEADACHE
The bones of the skull and brain substance are insensitive to pain because they lack pain sensitive nerve fibers.
Pain is referred to the frontotemporal area of the skull, from the following structures:
The intracranial segment of the internal carotid artery.
The proximal few centimeters of the anterior and middle cerebral arteries.
A portion of the cerebral veins and venous sinuses.
The middle meningeal artery.
The superficial temporal artery.
The previously mentioned structures contain pain sensitive nerves with the nociceptors at their ends. The latter can be stimulated by stress, muscular tension, dilated blood vessels and other triggers of headache. Once stimulated, the nociceptor sends a message up the length of the nerve fiber to the nerve cells in the brain, signaling that a part of the body hurts.
When is Headache a Warning of a More Serious Condition?
Migraine is a risk factor for cerebral stroke, particularly in young women, Thus, the best treatment consists of adequate control of migraine attacks and the avoidance of migraine drugs with marked vasoconstrictive action.
Familial hemiplegic migraine (FHM) is an autosomal dominant condition. Attacks start in childhood, adolescence, or early adulthood.
Migranous infarction is reported due to severe diffuse intracranial major arterial vasospasm.
Brain hemorrhage, might be related to vascular lesion brought about by ischemia secondary to vasospasm.
Intracranial vascular malformations (IVM)
Carotid artery stenosis
Occipital lobe tumor.
Clinical features that suggest the benign nature of a migraine attack.
Precipitation by menstruation
Amelioration with sleep.
Amelioration during pregnancy
Appearance after sustained exertion.
Triggers such as alcohol, odors, foods, or changes in the weather.
Trigger Factors of Migraine
Stress: The onset of attacks is usually during the period of calm immediately after such moments of stress.
Dental problems: When indicated, operations should be done.
Weather changes: Older migraine sufferers appear particularly vulnerable to this effect.
Cheese, chocolate, wine and beer sensitivity
Gastrointestinal inflammation: Some of the children suffering from migraine with or without aura have been found to have oesophygitis, gastritis of corpus, antral gastritis or duodenitis.
Female sex hormones fluctuations: these fluctuations may trigger, intensify, or alleviate migraine.
Minor trauma to the head or whiplash neck injury
Low back pain: due to increased muscle tension, psychosocial factors, and analgesic overuse.
Migraine and the eating disorders, particularly bulimia nervosa.
Nitric oxide (NO)
A Common denominator, namely, high levels of blood lipids and free fatty acids are underlying factor in the development of migraine headaches. Biological states that may cause increases in free fatty acids and blood lipids trigger migraine attack.
MECHANISMS OF MIGRAINE
The effect of the trigger factors on migraine prone patients:
Increased level of circulating vasoactive amines that causes constriction of the cortical microcirculation and focal brain ischemia. The reduced cerebral blood flow to the brain leads to depression of the brain nerve cells (neurons) activity with secondary aura and focal neurologic symptoms.
Decreased level of plasma endothelin-1 (A powerful vasoconstrictive agent) leads to vasodilatation of extracranial, middle meningeal and cerebral arteries that causes the headache phase.
Increased blood level of catecholamines which causes increased level of plasma free fatty acids and secondary platelet aggregation and release of serotonin which together with bradykinin and histamine causes sterile inflammatory response around the brain vessels. As a result of the altered immune response in migraine patients, the migration of Opioid-containing immune cells (brain pain controlling system) to the inflamed sites is delayed which causes an increase of the migraine pain.
Hereditary abnormality of the mitochondrial brain oxidative system, magnesium deficiency and abnormal preseynaptic calcium channels makes the brain nerve cells vulnerable to the trigger factors and causes excessive nerve cell discharge that opens the pain gait and give rise to spontaneous pain in the head and neck.
1. Sumner H. Salan U. Knight D W. Hoult J R S . Biochemical Pharmacology 43 (11). 1992. 2313-2320.
2. Marles, R. J. Kaminski, J. Arnason, J. T. Pazos-Sanou, L. Heptinstall, S. Fischer, N. H. Crompton, C. W. Kindack, D. G. Awang, D. V. C. Journal of Natural Products. 1992. 55: 8, 1044-1056.
3. Weber JT. Oconnor MF. Hayataka K. Colson N. Medora R. Russo EB. Parker KK. Journal of Natural Products. 60(6):651-653, 1997 Jun.
4. Barsby, R. W. J. Salan, U. Knight, D. W. Hoult, J. R. S. Planta Medica. 1993. 59: 1, 20-25
5. Vogler BK. Pittler MH. Ernst E. Cephalalgia. 18(10):704-708, 1998 Dec.
6. Palevitch D. Earon G. Carasso R. Phytotherapy Research. 11(7):508-511, 1997 Nov.
7. Peake P W. Pussell B A. Martyn P. Timmermans V. Charlesworth J A. International Journal of Immunopharmacology 13 (7). 1991. 853-858.
8. Schulz, H. Jobert, M. Hubner, W. D. Phytomedicine. 1998. 5: 6, 449-458.
9. (Yang Z. Copolov DL. Lim AT. Brain Research. 706(2):243-8, 1996 Jan 15).
10. Grimble R F. International Journal for Vitamin & Nutrition Research 67(5). 1997. 312-320.
11. Miller, T. Wittstock, U. Lindequist, U. Teuscher, E. Planta Medica. 1996. 62: 1, 60-61.
12. Bhunia C. Mukherjee M. Chatterjee P C. Indian Journal of Physiology & Allied Sciences 49(4). 1995. 208-211.
13. Yoshikawa M. Shimada H. Saka M. Yoshizumi S. Yamahara J. Matsuda H. Chemical & Pharmaceutical Bulletin (Tokyo) 45(3). 1997. 464-469.
14. Viola H. Wolfman C. Stein M L D. Wasowski C. Pena C. Medina J H. Paladini A C. Journal of Ethnopharmacology 44 (1). 1994. 47-53.
15. (Ustdal M. Dogan P. Soyuer A. Terzi S. Biomedicine & Pharmacotherapy. 43(9):687-91, 1989).
16. (Mauskop A. Altura BM.. Clinical Neuroscience. 5(1):24-7, 1998).
17. Stapleton P P. O'Flaherty L. Redmond H P. Bouchier Hayes D J. Journal of Parenteral & Enteral Nutrition 22(1). 1998. 42-48.
18. Michalk D V. Wingenfeld P. Licht C. Amino Acids (Vienna) 13(3-4). 1997. 337-346.
19. McCarty MF. Medical Hypotheses. 47(6):461-6, 1996 Dec.
20. Schoenen J. Jacquy J. Lenaerts M. Neurology 50(2). 1998. 466-470.
21. Covelli V. Maffione A B. Munno I. Jirillo E. Journal of Clinical Laboratory Analysis 4 (1). 19.
22. Grimble R F. International Journal for Vitamin & Nutrition Research 67(5). 1997. 312-320.
23. Jarisch R. Wantke F. International Archives of Allergy & Immunology. 110(1):7-12, 1996 May).
Migraine and its accompanying symptoms, complications, warning signs and mechanisms have been extensively studied before designing MIGRACELL. The scientific facts about the herbal ingredients of this remedy have been studied very carefully, with evidence of risks and benefits being made available to consumers.
The MIGRACELL cream is composed of completely natural ingredients that act synergistically. It is applied to the site of pain and nasal mucus membrane. It has the ability to penetrate the skin, the mucous membrane and the fine capillary walls to blood circulation to exert abortive and prophylactic effects in migraines and headaches without side effects.
THE MECHANISMS OF MIGRACELL ACTION
Regulates the altered immune response common with migraines, to activate the brain opiate system and control the pain.
Exhibits sedative and anxiolytic action.
Inhibits the contractile response of the vascular smooth muscles, relieves the vasospasm and improves the brain circulation that is always diminished during migraine attacks.
Stops the inflammatory response around the neurovascular system of the brain that is responsible for the migraine pain, through its anti-inflammatory action.
Inhibits platelet aggregation that might cause cerebral occlusion and neurological complications.
Inhibits the release of serotonin and histamine
Improves the mitochondrial energy metabolism which plays an important role in migraine pathogenesis.
Dampens neuronal hyperexcitation, increases tolerance to focal hypoxia, stabilizes platelets and lessens sympathetic outflow.
Inhibits arachidonic acid (eicosanoid) metabolism.
Feverfew, Tanacetum Parthenium.
Balm, Melissa officinalis, Labiatae
Chamomile, Matricaria recutita, compositae.
Jamaican Dogwood, Piscidia erythrina, Legminosae.
Linden, Tilia tomentosa Moench, Tiliaceae.
Feverfew, Tanacetum Parthenium compositae
Leaves or infusions of Feverfew, Tanacetum Parthenium, have long been used as a folk remedy for fever, arthritis and migraine. Feverfew contains a complex mixture of sesquiterpene lactone and non-sesquiterpene lactone, which are inhibitors of eicosanoid synthesis of high potency, and that these biochemical actions may be relevant to the claimed therapeutic actions of the herb (1).
Extracts of the herb Feverfew was found to inhibit human blood platelet aggregation and secretion of serotonin (14C5-HT) induced in-vitro by arachidonic acid and thromboxane and it has been concluded that this may relate to the beneficial effects of Feverfew in migraine (2).
A bioassay was developed to assess the in vitro activity of T. Parthenium and its inhibitory effect on the release of serotonin from bovine blood platelets. Inhibition of serotonin release was shown to be significantly correlated with the content of the germacranolide sesquiterpene lactone, parthenolide (3). The structures of two series of sesquiterpene lactones (the 'alpha'-series 11, 12 and 16 and the 'beta'-series 15, 17 and 18) present in the herb Feverfew have been revised in the light of both X-ray analysis and chemical correlation. The activity of some of these metabolites as well as of the major sesquiterpene lactone present in Feverfew, as inhibitors of human blood platelet function has been determined, The possible relevance of this effect to migraine prophylaxis by Feverfew has been concluded by some authors (4).
Studies showed that parthenolide may be a low-affinity antagonist at 5HAT(histamine) receptors.
In vitro experimental studies showed that extracts of fresh leaves of Feverfew caused dose- and time-dependent inhibition of the contractile responses of the smooth vascular muscles. This inhibitory effects was concluded to be due to Parthenolide (6) and its effect on the contractile responses of the smooth vascular muscles could be a factor in the ability of Feverfew extract to reverse the cerebral vasospasm that occurs in migraine attacks and sometimes leads to cerebral ischemia.
Studies showed that the mean frequency of chromosomal aberrations in the Feverfew user group was lower than that in the non-user group both in terms of cells with breaks (2.13% vs. 2.76%) and in terms of cells with all aberrations (4.34% vs. 5.11%). This difference was small and not significant (7), however, this observation merit further studies to see whether the Feverfew has any effect on the chromosomal aberration 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 (8).
One of the clinical trials was to assess the effectiveness of Feverfew as a prophylactic therapy for migraine; a double-blind placebo controlled crossover trial was conducted for a period of 4 months. Fifty-seven patients who attended an outpatient pain clinic were selected at random and divided into two groups. Both groups were treated with Feverfew in the preliminary phase (phase 1), which lasted 2 months. In the second and third phases, which continued for an additional 2 months, a double blind placebo-controlled crossover study was conducted. The results showed that Feverfew caused a significant reduction in pain intensity compared with the placebo treatment. Moreover; a profound reduction was recorded concerning the severity of the typical symptoms that are usually linked to migraine attacks, such as vomiting, nausea, sensitivity to noise and sensitivity to light. Transferring the Feverfew-treated group to the placebo treatment resulted in an augmentation of the pain intensity as well as an increase in the severity of the linked symptoms. In contrast, shifting the placebo group to Feverfew therapy resulted in a reduction of pain intensity as well as the severity of the linked symptoms (9).
Balm, Melissa officinalis, Labiatae
Rosmarinic acid (RA), a naturally occurring extract from Melissa officinalis, inhibits several complement-dependent inflammatory processes (11).
The sedative effects of Melissa officinalis extracts was proved by quantitative EEG analysis and by self-assessment (12)
It has been proved by experimental analysis that Melissa officinalis, contained high concentrations of total ascorbic acid (approximately equal to 300 mg/100 g FW) and relatively high ascorbate oxidase activity (10.1-21.1 micro mol min-1 g FW-1) (13). Besides acting as an important cofactor in the modulation of the biosynthesis of catecholamine, ascorbic acid (AA) has an active role in the post-translational modification of neuropeptides. AA in modulates the secretion of immunoreactive beta-endorphin (ir-beta EP) (14). As a result of the latter action it stimulate the brain opiate system for controlling the pain.
An important function of Ascorbic acid is that it exerts anti-inflammatory effects, which was proved by studies in man and animals.
In humans, supplementation with ascorbic acid enhances a number of aspects of lymphocyte function (blood cells responsible for the immune response) (15).
In Europe, M. officinalis is used to treat nervous disorders. Experimental studies showed that it exhibited significant analgesic activity(16 )
Chamomile, Matricaria recutita, compositae.
It has been found that en-yne dicycloether one of the constituents of the essential oil of C. recutita) could partly inhibit protamine sulfate-induced degranulation (histamine release) of mast cells (17).
Chamomil extract also exerts anti-inflammatory activity (18).
Jamaican Dogwood, Piscidia erythrina, Legminosae.
Some of the Lectins prepared from the Leguminosae seeds extracts have been tested in vitro against human platelet and has been found to inhibit platelet aggregation (19).
Linden, Tilia tomentosa Moench, Tiliaceae
Components prepared from Tiliaceae were found to inhibit the histamine release induced by antigen-antibody reaction (20).
Tilia species are traditional medicinal plants widely used in Latin America as sedatives and tranquilizers. Studies showed that it has clear anxiolytic effect (21).
The results of salmon Calcitonin treatment on migraine pain have been studied to verify the mechanism by which Calcitonin induces analgesia. The circulating levels of beta-endorphin, ACTH, and cortisol in patients with migraine during the headache-free period increased after the Calcitonin administration and the maximum increase was obtained in beta-endorphin levels (22).
The importance of magnesium in the pathogenesis of migraine headaches is clearly established by a large number of clinical and experimental studies. Magnesium concentration has an effect on serotonin receptors, and a variety of other migraine related receptors and neurotransmitters. 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 a rapid and sustained relief of an acute migraine in such patients. Two double-blind studies suggest that chronic oral magnesium supplementation may also reduce the frequency of migraine headaches (23).
Taurine (2-aminoethane sulphonic acid), a ubiquitous beta-amino acid is conditionally essential for man. It is not utilized in protein synthesis but found free or in some simple peptides. Derived from methionine and cysteine metabolism, Taurine is known to play a vital role in numerous physiological functions. Some of the roles with which Taurine has been associated include osmoregulation, antioxidation, detoxification and stimulation of glycolysis and glycogenesis (24).
Taurine administered during hypoxia markedly reduced cellular deterioration due to hypoxia and reoxygenation and led to a significantly greater recovery of cellular function following the hypoxic insult. The responsible mechanisms for the beneficial effects were an improvement in osmotic status and calcium homeostasis and an induction in cellular growth despite oxygen deficiency and reoxygenation. Free oxygen radical generation and lipid membrane peroxidation were not reduced by Taurine. Taurine acted as a potent endogenous agent with multifactorial effects against cellular damage due to hypoxia and reoxygenation (25).
Increased tissue levels of Taurine, as well as increased extracellular magnesium, could be expected to dampen neuronal hyperexcitation, counteract vasospasm, increase tolerance to focal hypoxia and stabilize platelets; taurine may also lessen sympathetic outflow. Thus it is reasonable to speculate that supplemental magnesium taurate will have preventive value in the treatment of migraine (26).
It has been found that Riboflavin regulates mitochondrial oxidative metabolism, which may play a role in migraine pathogenesis. Riboflavin (400 mg) was compared to placebo in 55 patients with migraine in a randomized trial of 3 months duration. Riboflavin was superior to placebo in reducing attack frequency (p = 0.005) and headache days (p = 0.012) (27).
Clinical data in migraine showed altered immune status in patients during migraine attacks (28). Riboflavin participate in the maintainance of glutathione status,that is a major endogenous antioxidant and is important for lymphocyte replication. It regulates the altered immune status in migraine. Deficiencies in Riboflavin reduce cell numbers in lymphoid tissues of experimental animals and produce functional abnormalities in the cell mediated immune response (29).
Vitamin B6 (Pyridoxal Phosphate)
As supportive treatment, a vitamin B6 (pyridoxal phosphate) substitution appears useful in histamine-intolerant patients, as pyridoxal phosphate seems to be crucial for diamine oxidase activity, an enzyme essential for histamine degradation and which is deficient in those patients. (30).
1. Sumner H. Salan U. Knight D W. Hoult J R S. Biochemical Pharmacology 43 (11). 1992. 2313-2320.
2. Groenewegen W A. Heptinstall S. Journal of Pharmacy & Pharmacology 42 (8). 1990. 553-557.
3. Marles, R. J. Kaminski, J. Arnason, J. T. Pazos-Sanou, L. Heptinstall, S. Fischer, N. H. Crompton, C. W. Kindack, D. G. Awang, D. V. C. Journal of Natural Products. 1992. 55: 8, 1044-1056.
4. Hewlett MJ. Begley MJ. Groenewegen WA. Heptinstall S. Knight DW. May J. Salan U. Toplis D. Journal of the Chemical Society. Perkin Transactions 1. (16):1979-1986, 1996 Aug 21.
5. Weber JT. Oconnor MF. Hayataka K. Colson N. Medora R. Russo EB. Parker KK. . 60(6):651-653, 1997 Jun.
6. Barsby, R. W. J. Salan, U. Knight, D. W. Hoult, J. R. S. Planta Medica. 1993. 59: 1, 20-25.
7. Anderson D. Jenkinson PC. Dewdney RS. Blowers SD. Johnson ES. Kadam NP. Human Toxicology. 7(2):145-52, 1988 Mar.
8. Vogler BK. Pittler MH. Ernst E. Cephalalgia. 18(10):704-708, 1998 Dec.
9. (Palevitch D. Earon G. Carasso R. Phytotherapy Research. 11(7):508-511, 1997 Nov.
10. Mustafa T. Srivastava K C. Journal of Ethnopharmacology 29 (3). 1990. 267-274.
11. Peake P W. Pussell B A. Martyn P. Timmermans V. Charlesworth J A. International Journal of Immunopharmacology 13 (7). 1991. 853-858.
12. Schulz, H. Jobert, M. Hubner, W. D. Phytomedicine. 1998. 5: 6, 449-458.
13. Yamawaki, K. Morita, N. Murakami, K. Murata, T. Journal of the Japanese Society for Food Science and Technology. 1993. 40: 9, 636-640.
14. Yang Z. Copolov DL. Lim AT. Brain Research. 706(2):243-8, 1996 Jan 15).
15. Grimble R F. . International Journal for Vitamin & Nutrition Research 67(5). 1997. 312-320.
16. Soulimani, R. Younos, C. Fleurentin, J. Mortier, F. Misslin, R. Derrieux, G. [French] Plantes Medicinales et Phytotherapie. 1993. 26: 2, 77-85.
17. Miller, T. Wittstock, U. Lindequist, U. Teuscher, E. Planta Medica. 1996. 62: 1, 60-61.
18. Loggia, R. della. Carle, R. Sosa, S. Tubaro, A. Planta Medica. 1990. 56: 6, 657-658.
19. Bhunia C. Mukherjee M. Chatterjee P C. Indian Journal of Physiology & Allied Sciences 49(4). 1995. 208-211.
20. Yoshikawa M. Shimada H. Saka M. Yoshizumi S. Yamahara J. Matsuda H. Chemical & Pharmaceutical Bulletin (Tokyo) 45(3). 1997. 464-469.
21. Viola H. Wolfman C. Stein M L D. Wasowski C. Pena C. Medina J H. Paladini A C. Journal of Ethnopharmacology 44 (1). 1994. 47-53.
22. (Ustdal M. Dogan P. Soyuer A. Terzi S. Biomedicine & Pharmacotherapy. 43(9):687-91, 1989).
23. (Mauskop A. Altura BM. Clinical Neuroscience. 5(1):24-7, 1998).
24. Stapleton P P. O'Flaherty L. Redmond H P. Bouchier Hayes D J. Cornell Journal of Parenteral & Enteral Nutrition 22(1). 1998. 42-48.
25. Michalk D V. Wingenfeld P. Licht C. . Amino Acids (Vienna) 13(3-4). 1997. 337-346.
26. McCarty MF. Medical Hypotheses. 47(6):461-6, 1996 Dec.
27. Schoenen J. Jacquy J. Lenaerts M. Neurology 50(2). 1998. 466-470.
28. Covelli V. Maffione A B. Munno I. Jirillo E. Journal of Clinical Laboratory Analysis 4 (1). 19.
29. Grimble R F. International Journal for Vitamin & Nutrition Research 67(5). 1997. 312-320.
30. (Jarisch R. Wantke F. International Archives of Allergy & Immunology. 110(1):7-12, 1996 May).
- November 28, 2016
- Elena M