Laboratory investigation

Patients with typical migraine:
Neuroimaging or laboratory studies are unnecessary in the routine diagnosis of typical migraine; however, it is sometimes important to obtain an electrocardiogram and baseline laboratory studies such as a hemogram and a chemistry profile before initiation of therapy to ensure the safety of intervention. 

Patient with either a new onset of headache or a change in a previously stable headache profile after 50 years of age:
Erythrocyte sedimentation rate, Cranial neuroimaging, high quality enhanced computed tomography. In the case of a suspected posterior fossa lesion in patients with a progressive headache syndrome, papilledema, or abnormal findings on neurologic examination, magnetic resonance imaging should be done. If subarachnoid hemorrhage is suspected, then examination of the cerebrospinal fluid with measurement of the opening pressure is indicated after an appropriate imaging study has excluded contraindication to lumbar puncture. In cases of suspected bacterial meningitis, neuroimaging studies do not need to be performed before a lumbar puncture in the absence of papilledema and focal neurologic findings. Cerebral angiography is indicated in cases of suspected central nervous system vasculitis, arterial dissection, cerebral aneurysm, or arteriovenous malformation. 

PHARMACOLOGIC TREATMENT OF MIGRAINE (41).
Effective management of migraine includes establishing realistic expectations, patient reassurance, and education.

The choice of medication (abortive, symptomatic) for an acute attack depends on such factors as:
 

The severity of the attack.
The presence or absence of vomiting
The time of onset to peak pain.
The rate of bioavailability of the drug.
The comorbid medical conditions, and side-effect profile.

 

Effective agents for acute attacks:
 

Simple or combination analgesics.
Non-esteroidal anti-inflammatory drugs.
Ergot derivatives.
Selective serotonin agonists.

 

Preventive (prophylactic, interval) medication depends primarily on comorbid medical conditions and side-effect profile. 

Preventive agents:
 

Beta-adrenergic blockers.
Calcium channel blockers.
Tricyclic antidepressants,.
Anticonvulsant medications.
Serotonin antagonists.

 

It is recommended to explain to the patients that they were born with a sensitive neurovascular system that overreacts to internal changes or external stimuli and that the condition can probably be controlled with non-pharmacological and appropriate pharmacological treatment. Patients are more likely to be active participants in their treatment if they have a better understanding of their condition. Patients may be referred to the Migraine Association of Canada for information and support and may benefit from referral to local self-help groups.

It is important to avoid analgesic overuse as it causes rebound headache. Symptomatic medications, whether prescribed or over-the-counter, when taken on a daily or almost daily basis can result in a chronic daily headache syndrome that can be refractory to treatment. An under-appreciated point is that excessive use of symptomatic medications on a daily basis may render prophylactic and symptomatic medications ineffective. 

Symptomatic Therapy. 
Symptomatic therapy is the mainstay of migraine management. Effective treatment of the acute migraine attack should terminate or decrease the symptoms of the attack. 
· Simple Analgesics. It is recommended to use of ASA and acetaminophen as the treatment of choice for mild to moderate migraine attacks. Enteric-coated ASA , should not be used for migraine because of delayed onset of action. Effervescent preparations are more effective due to more rapid absorption 

Combination Analgesics. 
Two frequently used combination drugs effective in the treatment of mild to moderate migraine attacks contain either isometheptene with acetaminophen and dichloralphenazone or ASA and acetaminophen with butalbital and caffeine. Both combinations can cause a medication-induced or analgesic rebound headache if used frequently. Therefore, we limit use of these agents to no more than 2 days per week. 

Nonsteroidal Anti-Inflammatory Drugs 
NSAIDs is considered the first-line therapy for mild to moderate migraine attacks. Selected examples include naproxen sodium, ibuprofen, ketorolac, and indomethacin, NSAIDs are contraindicated in patients with active ulcer disease. Potential side effects include nausea, abdominal pain, diarrhea, light-headedness, somnolence, and fluid retention, as well as hepatic toxicity and nephrotoxicity. 

Ergot Derivatives 
Ergotamine Tartrate is effective symptomatic treatment of moderate to severe migraine attacks that fail to respond to simple or combination analgesics. Although both oral and suppository dosing are available, plasma levels are 20 times higher with rectal administration. A crucial and often neglected point is that a sub-nauseating dose must be used. Such a dose can range from one-quarter to a whole ergotamine tartrate suppository. 
Ergotamine tartrate is contraindicated in the following conditions: women considering pregnancy and during pregnancy; sepsis; inadequately controlled hypertension; cerebral, coronary, and peripheral vascular disease; as well as hepatic and renal insufficiency. Major side effects include abdominal cramps, paresthesias, and nausea. The development of chest tightness after use of ergotamine tartrate is a cause for concern and necessitates discontinuation of use of the medication and obtainment of an appropriate medical referral. Patients should limit their use of ergotamine tartrate to no more than 2 days per week and to take no more than 10 mg per week. Overuse can produce ergotism and chronic daily headaches. 

Dihydroergotamine 
Unlike ergotamine tartrate, DHE minimally constricts peripheral arteries yet is a potent venoconstrictor. Unlike ergotamine, DHE does not result in physical dependence. As with ergotamine tartrate, the subnauseating dose must be determined. Contraindications to the use of DHE are similar to those for ergotamine tartrate. 

Sumatriptan 
Sumatriptan, a selective 5-HT sub 1 receptor agonist, has been approved for treatment of acute migraine. Headaches recur in up to 40% of patients probably because of the relative short half-life of 2 hours. Sumatriptan administered subcutaneously has a rapid onset of action, with statistically significant relief being obtained in 10 minutes. Sumatriptan remains efficacious even if given well into the headache phase. Its beneficial effects on associated gastrointestinal symptoms eliminate the need for coadministration of an antiemetic. sumatriptan administered at the onset of a migraine aura has no benefit. Oral sumatriptan therapy, which was recently approved by the FDA, is similarly effective but has a slower onset of action. 

Sumatriptan is contraindicated in patients with inadequately controlled hypertension, ischemic heart disease, Prinzmetal's angina, and complicated migraine including vertebrobasilar migraine, as well as in pregnant patients. Side effects of subcutaneous sumatriptan therapy include discomfort at the injection site, diffuse burning, tingling, and, occasionally, neck or chest pain (or both). postmenopausal women, men older than age 40 years, and patients with vascular risk factors such as hypertension, hypercholesterolemia, obesity, diabetes, smoking, and a strong family history of vascular disease without a prior assessment for unrecognized coronary artery disease (CAD). 

Phenothiazines 
Several controlled studies have demonstrated the efficacy of intravenous chlorpromazine and prochlorperazine therapy. However care must be taken to ensure adequate hydration before use of intravenous chlorpromazine therapy. DHE and prochlorperazine are miscible and can be combined in a single syringe. 

Corticosteroids 
Prednisone, hydrocortisone, or methylprednisolone can be considered for prolonged migraine attacks that are refractory to the more standard treatment options. 3- to 5-day course of outpatient oral corticosteroid therapy is sometimes used for particularly refractory migraine attacks. Parentally administered corticosteroids are useful for terminating a severe, prolonged migraine attack when there are contraindications to ergot preparations or when ergot preparations have failed to provide relief. 
Repeated use of corticosteroid is contraindicated as it causes hormonal implance, cushing's disease, osteoporosis, diabetes hypertension and lower the immune response to infections.

Narcotic Analgesics 
Although meperidine is often used as an abortive agent in many emergency departments, clinical trials to support widespread use of this narcotic agent are lacking. 

Prophylactic Therapy 
Criteria for selecting patients for prophylactic treatment
 

Attacks that occur more than 2 to 3 times a month.
Attacks that last more than 48 hours.
Attacks that are severe.
If the patient is unable psychologically to cope with the attacks.
Treatment of an acute attack provides inadequate relief or therapy produces serious side effects 
Attacks occur after prolonged aura. 
Several additional factors must be considered before prophylactic treatment can be initiated. 

 

Because of the potential teratogenic effect of the prophylactic agents, women of childbearing age should be using a reliable type of birth control. Prophylactic therapy should be considered in patients taking excessive amounts of symptomatic medications, which lead to rebound headaches. 

Several pitfalls have been identified in migraine prophylaxis. The dose may be inadequate, either insufficient or excessive--it is prudent to "start low and go slow." The trial regimen of treatment may be inadequate. The minimal time interval for migraine prophylaxis before a beneficial effect is noted is generally 1 to 2 months, especially when calcium channel blockers are being used.

Although elimination of migraine is a worthy therapeutic goal, in actuality, medications for Prophylaxis are seldom more than 55 to 65% effective. The medications used include beta-blockers, calcium channel blockers, tricyclic anti-depressants, anticonvulsants, serotonin antagonists, NSAIDs, and MAO inhibitors. 

Beta-Adrenergic Blocking Agents. 
Beta-Blockers remain the treatment of choice for prophylaxis of migraine, especially if the patient has comorbid hypertension or anxiety. Examples of beta-blockers include propranolol, nadolol, atenolol, timolol, and metoprolol. 
Use of beta-blockers should never be discontinued abruptly. Contraindications include asthma, insulin-dependent diabetes mellitus, heart failure, heart block, pregnancy, and Raynaud's phenomenon. Side effects, including lethargy, depression, impotence, and hair loss, limit use of beta-blockers in many people. 

Calcium Channel Blockers. 
Although calcium channel blockers are considered by some investigators as first-line therapy for migraine prophylaxis, the evidence in support of their efficacy is underwhelming. Some investigators have suggested that verapamil has a marginal benefit in decreasing the frequency of migraine attacks. Several trials have used nifedipine and nimodipine in the treatment of migraine. Nifedipine often causes a dull persistent headache, and nimodipine is approved only for use in subarachnoid hemorrhage and is too expensive to be used as a long-term agent. Contraindications include hypotension, heart block, sick sinus syndrome, and atrial fibrillation and flutter. Constipation can be a troublesome side effect. 

Tricyclic Antidepressants. 
Amitriptyline is useful for migraine prophylaxis, particularly in patients with coexisting depression, tension headaches, or insomnia. Nortriptyline is as efficacious as amitriptyline, but it has not been formally studied. Contraindications include glaucoma, urinary retention, and cardiovascular disease, particularly ventricular conduction abnormalities. 

Anticonvulsants 
Divalproex sodium has been shown to be an effective prophylactic agent for migraine in several double blind, placebo-controlled studies. This agent can be considered first-line therapy for patients with coexisting seizures, mania, or anxiety. Idiosyncratic reactions can include hepatitis or pancreatitis.; clinical monitoring is thought to be the best method for long-term management. 

Serotonin Antagonists 
Methysergide, a semisynthetic ergot, is effective in preventing migraine attacks. Contraindications include CAD, gastritis, uncontrolled hypertension, connective tissue disease, and pregnancy. The major concern of methysergide is the side-effect profile, which includes potential idiosyncratic fibrotic complications. If the patient's symptoms are relieved substantially, use of methysergide can be slowly tapered after approximately 4 months. The Physicians' Desk Reference recommends a medication-free interval of 3 to 4 weeks after 6 months of continuous treatment. For patients who receive methysergide for 6 months or longer, periodic monitoring should include auscultation of the heart, chest roentgenography, computed tomography or magnetic resonance imaging of the abdomen, and urinalysis. As with all medications, methysergide should be prescribed with complete knowledge of the side-effect profile. 

Nonsteroidal Anti-Inflammatory Drugs. 
Although NSAIDs can be used for migraine prophylaxis, potential gastrointestinal and renal complications limit its recommendation to short-term use. It is important to monitor the serum creatinine. 

Monoamine Oxidase Inhibitors 
MAO inhibitors have been found to be effective in patients with migraine headaches refractory to more standard treatment. Before initiation of phenelzine, a dietary consultation is advised. Patients must be given a list of medications and foods that they should avoid, including over-the-counter medications, particularly nasal decongestants. 

NONPHARMACOLOGIC MANAGEMENT OF MIGRAINE(42)

Augmentation of the use of non-pharmacological therapies for the acute and prophylactic management of migraine is likely to lead to substantial benefits in both human and economic terms. Both the avoidance of migraine trigger factors and the use of non-pharmacological therapies have a part to play in overall migraine management. 
Many of the non-pharmacological therapies are based on the theoretic concept of migraine as resulting from neurochemical instability within the brain. These approaches, which are often "biobehaviouristic," may be complementary or adjunctive to pharmacological treatment or may provide an alternative to it. 

Patient education
Patient education refers to "the information provided by health professionals to headache patients. Patient education is a necessary component of any treatment plan, and it is recommended that it include the following items:
 

The diagnosis of migraine should be given clearly and confidently after the appropriate history-taking and clinical examination and, when necessary, after investigations have been completed.
Patients should be reassured that they do not have a serious underlying cause for the headaches, such as a brain tumor. 

 

Acute non-pharmacological treatment
Most of the non-pharmacological measures found to be effective in alleviating an acute migraine headache.
 

The application of cold or pressure to the head has been assessed as valuable.
Reduction of activity and of sensory input in a quiet or dark environment and attempts to sleep. 
Relaxation therapy, hypnosis, transcutaneous electrical stimulation, acupuncture, and occipital or supraorbital nerve blockade have also been used in the acute situation.

 

BIOBEHAVIOURAL MEASURES
Biofeedback
Biofeedback refers to the use of monitoring instruments to detect, amplify and display internal physiologic processes on-line, so that the patient may learn to alter these processes at will. Various types of biofeedback have been used successfully as prophylaxis for migraine. 

A report denying the value of biofeedback has also been published, (36) and it is not possible to predict which patients are most likely to benefit. The effect of combining biofeedback with pharmacological therapy has seldom been studied. Biofeedback requires a substantial time commitment on the part of the patient, which may limit its use. 

Relaxation therapy
Biobehavioural approach to migraine comprising relaxation techniques (including progressive muscular relaxation, breathing exercises or directed imagery) may or may not reduce the frequency of episodes. Meta-analysis suggests that relaxation is as effective as biofeedback. Where a treatment effect has been reported, it may be enhanced by the addition of prophylactic agents such as beta-blocking drugs. The usual goal of relaxation therapy is the development of long-term prophylaxis rather than the reduction of pain during an acute attack. However, a few patients can abort a slowly evolving migraine using these techniques. 

Cognitive-behavioural therapy
Cognitive-behavioural therapy (CBT) is designed to help patients identify and modify maladaptive responses that may trigger or aggravate a migraine headache. The role of emotional reactivity as a trigger for migraine is considered to be pertinent in many patients, who may indulge in self-blame, hopelessness and catastrophic thinking. CBT is based on the principle that anxiety and distress are aggravators of an evolving migraine headache; it attempts to introduce a more adaptive approach as well as to help develop a specific action plan. Stress-management training is often part of this approach. CBT is usually combined with other behavioural therapies but has been shown to be effective on its own Individual therapist, group and self-help programs have been used, with variable effects. However, as with other behavioural therapies, such factors as availability, cost, patient acceptance and the time commitment required may restrict their use. 

Psychotherapy
It is suggested that psychiatric referral of patients with migraine is indicated solely for the presence of a coexistent psychiatric disorder. However, referral to a psychologist to improve stress management may be appropriate in selected cases. The use of psychosocial interventions appears to be of modest value Psychiatric referral of patients with migraine is not indicated except in the presence of a coexistent psychiatric disorder. 

Hypnosis 
Hypnosis may reduce distressing sensory input as it does in other pain disorders and may have a placebo effect. It was more effective than prochlorperazine in one randomized controlled trial, and a meta-analysis of largely uncontrolled studies also suggested benefit when hypnosis was combined with CBT. However hypnosis may have a limited role in the management of migraine in a small subgroup of patients who are both willing and suitable subjects. 

Physical measures

Complementary or alternative therapies may be described as interventions that lack either a valid scientific basis or adequate documentation of their effectiveness in the treatment of specific conditions. Chiropractic, osteopathy and acupuncture have been used in the management of migraine but have rarely been subjected to trial, and evidence for the superiority of any one form of cervical manipulation is lacking. However it has been assumed that chiropractic manipulations reduced migraine frequency and severity while aerobic training may reduce the number but not the severity of migraine headaches. 

The value and cost-effectiveness of physiotherapy, osteopathy and chiropractic in the management of migraine have not yet been determined. It is therefore inappropriate for a physician to refer patients for such treatments, but patients who are strongly motivated to seek such help need not be dissuaded as long as they are made aware of the uncertain benefits so far recorded. 

Transcutaneous electrical stimulation and acupuncture
Transcutaneous electrical stimulation and have been claimed in small series to provide some relief from migraine. Patients who enquire about transcutaneous electrical stimulation and acupuncture should be made aware of the lack of firm evidence as to the benefits and cost-effectiveness of these treatments in the management of migraine

REFERENCES

Pryse-Phillips WE. Dodick DW. Edmeads JG. Gawel MJ. Nelson RF. Purdy RA. Robinson G. Stirling D. Worthington I. Guidelines for the non-pharmacological management of migraine in clinical practice. Canadian Headache Society ,CMAJ. 159(1):47-54, 1998 Jul 14.

(2)Capobianco DJ. Cheshire WP. Campbell JK. An overview of the diagnosis and pharmacologic treatment of migraine. Mayo Clinic Proceedings. 71(11):1055-66, 1996 Nov).

(3)Welch KM. Pathogenesis of migraine. Seminars in Neurology. 17(4):335-41, 1997.

(4) (Spierings EL. Symptomatology and pathogenesis of migraine. Journal of Pediatric Gastroenterology & Nutrition. 21 Suppl 1:S37-41, 1995).

(5) (Amery WK. Migraine and cerebral hypoxia: a hypothesis with pharmacotherapeutic implications. Cephalalgia. 5 Suppl 2:131-3, 1985 May).

(Young DB. Van Vliet BN. Migraine with aura: a vicious cycle perpetuated by potassium-induced vasoconstriction. Headache. 32(1):24-34, 1992 Jan).
Lanteri-Minet M. Desnuelle C. Migraine and mitochondrial dysfunction. Revue Neurologique. 152(4):234-8, 1996 Apr.
(Mauskop A. Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clinical Neuroscience. 5(1):24-7, 1998).

(Machelska H. Cabot PJ. Mousa SA. Zhang Q. Stein C. Pain control in inflammation governed by selectins. Nature Medicine. 4(12):1425-8, 1998 Dec).

(Leone M. Sacerdote P. D'Amico D. Panerai AE. Bussone G. Beta-endorphin concentrations in the peripheral blood mononuclear cells of migraine and tension-type headache patients . Cephalalgia. 12(3):154-7, 1992 Jun).

(Genazzani AR. Petraglia F. Facchini V. Facchinetti F. Cephalalgia. 3 Suppl 1:35-41, 1983 Aug).

(12)Vecsei L. Widerlov E. Ekman R. Kovacs K. Jelencsik I. Bozsik G. Kapocs G. (Suboccipital cerebrospinal fluid and plasma concentrations of somatostatin, neuropeptide Y and beta-endorphin in patients with common migraine. Neuropeptides. 22(2):111-6, 1992 Jun).


(13) Anselmi B. Tarquini R. Panconesi A. de Leonardis V. Perfetto F. Piluso A. Naldi E. Tarquini B. Serum beta-endorphin increase after intravenous histamine treatment of chronic daily headache. Recenti Progressi in Medicina. 88(7-8):321-4, 1997 Jul-Aug).

(14) (Doenicke A. Moss J. Toledano A. Hoernecke R. Lorenz W. Ostwald P. Administration of H1 and H2 antagonists for chemoprophylaxis: a double-blind, placebo-controlled study in healthy volunteers. Journal of Clinical Pharmacology. 37(2):140-6, 1997 Feb).

(15) (Jarisch R. Wantke F. Wine and headache. International Archives of Allergy & Immunology. 110(1):7-12, 1996 May).

(16)Geller EB. Wen PY. Migraine with aura as the presentation of leukemia. Headache. 35(9):560-2, 1995 Oct. 

(17) Komatsumoto S. Nara M. [Lower level of endothelin-1 in migraine with aura]. Rinsho Shinkeigaku - Clinical Neurology. 35(11):1250-2, 1995 Nov.

(18) Leira R. [Migraine due to infarct]. [Spanish] Neurologia. 12 Suppl 5:16-23, 1997 Dec.

(19) Ries S. Steinke W. Neff W. Schindlmayr C. Meairs S. Hennerici M. Ischemia-induced migraine from paradoxical cardioembolic stroke.European Neurology. 36(2):76-8, 1996.

(20)Joutel A. Tournier-Lasserve E. Bousser MG. [Hemiplegic migraine]. [Review] [French] Presse Medicale. 24(8):411-4, 1995 Feb 25.

(21)Sanin LC. Mathew NT. Severe diffuse intracranial vasospasm as a cause of extensive migrainous cerebral infarction. Comment in: Cephalalgia 1993 Aug;13(4):231 Cephalalgia. 13(4):289-92, 1993 Aug.

(22) Aldrey JM. Castillo J. Leira R. Suarez P. Sobrido MJ. Noya M. [Cerebral hemorrhage and migraine]. [Spanish] Revista de Neurologia. 24(126):183-6, 1996 Feb.

(23)Monteiro JM. Rosas MJ. Correia AP. Vaz AR. Migraine and intracranial vascular malformations Comment in: Headache 1994 May;34(5):287

(24) Narbone MC. Rao R. Grugno R. Pellicano M. A late 'migraine': the only symptom of an intrasellar aneurysm. Headache. 37(8):527-8, 1997 Sep.

(25) Micieli G. Bosone D. Tassorelli C. Zappoli F. Castellano AE. Nappi G. Internal carotid occlusion associated with migraine syndrome: a case study of a 22-year-old female. Functional Neurology. 11(1):45-51, 1996 Jan-Feb.
(26). Verma A. Rosenfeld V. Forteza A. Sharma KR. Occipital lobe tumor presenting as migraine with typical aura Comment in: Headache 1997 Feb;37(2):11)Headache. 36(1):49-52, 1996 Jan.
(27)Geller EB. Wen PY. Migraine with aura as the presentation of leukemia. Headache. 35(9):560-2, 1995 Oct.

(28)Niczyporuk-Turek A. [Factors contributing to so-called idiopathic headaches]. [Polish] Neurologia Neurochirurgia Polska. 31(5):895-904, 1997 Sep-Oct.

(29)Galiano L. Montiel I. Falip R. Asensio M. Matias-Guiu J. [Stress as a precipitating factor in migraine]. [Spanish] Revista de Neurologia. 23(122):830-2, 1995 Jul-Aug.

(30)Lunardon M. Barolin GS. [Odontogenic (concomitant) etiology of headache]. [German] Wiener Medizinische Wochenschrift. 147(15):365-8, 1997.

(31). Piorecky J. Becker WJ. Rose MS. Effect of Chinook winds on the probability of migraine headache occurrence.Headache. 37(3):153-8, 1997 Mar.

(32)Peatfield RC. Relationships between food, wine, and beer-precipitated migrainous headaches. Headache. 35(6):355-7, 1995 Jun.
(33)Mavromichalis I. Zaramboukas T. Giala MM. Migraine of gastrointestinal origin. European Journal of Pediatrics. 154(5):406-10, 1995 May.

(34) Silberstein SD. Migraine and women. The link between headache and hormones. Postgraduate Medicine. 97(4):147-53, 1995 Apr

(35) Szigethy A. Dienes L. The relation between atypical migraine and multiphasic oral contraceptives. Therapia Hungarica. 40(4):185-8, 1992.

(36)Weiss HD. Stern BJ. Goldberg J. Post-traumatic migraine: chronic migraine precipitated by minor head or neck trauma Comment in: Headache 1992 Mar;32(3):157-8 Headache. 31(7):451-6, 1991 Jul.
(37) Duckro PN. Schultz KT. Chibnall JT. Migraine as a sequela to chronic low back pain. Headache. 34(5):279-81, 1994 May.

(38)George MS. Is migraine related to the eating disorders?. International Journal of Eating Disorders. 14(1):75-9, 1993 Jul.
(39)Olesen J. Thomsen LL. Iversen H. Nitric oxide is a key molecule in migraine and other vascular headaches. Trends in Pharmacological Sciences. 15(5):149-53, 1994 May.

(40)(Bic Z. Blix GG. Hopp HP. Leslie FM. In search of the ideal treatment for migraine headache. Medical Hypotheses. 50(1):1-7, 1998 Jan).

(41)(Capobianco DJ. Cheshire WP. Campbell JK. An overview of the diagnosis and pharmacologic treatment of migraine. Mayo Clinic Proceedings. 71(11):1055-66, 1996 Nov).

MIGRACELL

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.

 

ACTIVE INGREDIENTS 
 

Feverfew, Tanacetum Parthenium.
Balm, Melissa officinalis, Labiatae
Chamomile, Matricaria recutita, compositae.
Jamaican Dogwood, Piscidia erythrina, Leguminosae.
Linden, Tilia tomentosa Moench, Tiliaceae. 
Salmon Calcitonin.
Magnesium.
Taurine.
Riboflavin.

 

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). 

Salmon Calcitonin
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). 

Magnesium
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
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). 

Riboflavin
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). 

REFERENCES

(1) Sumner H. Salan U. Knight D W. Hoult J R S. INHIBITION OF 5 LIPOXYGENASE AND CYCLOOXYGENASE IN LEUKOCYTES BY FEVERFEW INVOLVEMENT OF SESQUITERPENE LACTONES AND OTHER COMPONENTS. Biochemical Pharmacology 43 (11). 1992. 2313-2320. 

(2)Groenewegen W A. Heptinstall S. A COMPARISON OF THE EFFECTS OF AN EXTRACT OF FEVERFEW AND PARTHENOLIDE A COMPONENT OF FEVERFEW ON HUMAN PLATELET ACTIVITY IN-VITRO. 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. A bioassay for inhibition of serotonin release from bovine platelets. 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. 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.

(5)Weber JT. Oconnor MF. Hayataka K. Colson N. Medora R. Russo EB. Parker KK. ACTIVITY OF PARTHENOLIDE AT 5HT(2A) RECEPTORS. Journal of Natural Products. 60(6):651-653, 1997 Jun.

(6) Barsby, R. W. J. Salan, 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.

(7)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.

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

(9)Palevitch D. Earon G. Carasso R. FEVERFEW (TANACETUM PARTHENIUM) AS A PROPHYLACTIC TREATMENT FOR MIGRAINE - A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY Phytotherapy Research. 11(7):508-511, 1997 Nov.

(10) Mustafa T. Srivastava K C. GINGER ZINGIBER-OFFICINALE IN MIGRAINE HEADACHE. Journal of Ethnopharmacology 29 (3). 1990. 267-274.

(11) Peake P W. Pussell B A. Martyn P. Timmermans V. Charlesworth J A. THE INHIBITORY EFFECT OF ROSMARINIC ACID ON COMPLEMENT INVOLVES THE C5 CONVERTASE. International Journal of Immunopharmacology 13 (7). 1991. 853-858.

(12) Schulz, H. Jobert, M. Hubner, W. D. The quantitative EEG as a screening instrument to identify sedative effects of single doses of plant extracts in comparison with diazepam. Phytomedicine. 1998. 5: 6, 449-458.

(13)Yamawaki, K. Morita, N. Murakami, K. Murata, T. Contents of ascorbic acid and ascorbate oxidase activity in fresh herbs. Nippon Shokuhin Kogyo Gakkaishi = Journal of the Japanese Society for Food Science and Technology. 1993. 40: 9, 636-640.

(14)(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).

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

(16) 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.

(17)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. 

(18) 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. 

(19)Bhunia C. Mukherjee M. Chatterjee P C. Some observations on human platelet deaggregation by lectins. Indian Journal of Physiology & Allied Sciences 49(4). 1995. 208-211.

(20) Yoshikawa M. Shimada H. Saka M. Yoshizumi S. Yamahara J. Matsuda H. Medicinal foodstuffs: V. Moroheiya: (1): Absolute stereostructures of corchoionosides A, B, and C, histamine release inhibitors from the leaves of Vietnamese Corchorus olitorius L. (Tiliaceae). 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. Isolation of pharmacologically active benzodiazepine receptor ligands from Tilia tomentosa (Tiliaceae). Journal of Ethnopharmacology 44 (1). 1994. 47-53.

(22)(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).

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

(24)Stapleton P P. O'Flaherty L. Redmond H P. Bouchier Hayes D J. Cornell Univ. Med. Coll., P.O.Box 177, 1300 York Ave., New York, NY 10021, USA. Host defense: A role for the amino acid taurine? Jpen: Journal of Parenteral & Enteral Nutrition 22(1). 1998. 42-48.

(25) 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.

(26) McCarty MF. Magnesium taurate and fish oil for prevention of migraine. Medical Hypotheses. 47(6):461-6, 1996 Dec.

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

(28)Covelli V. Maffione A B. Munno I. Jirillo E. ALTERATIONS OF NONSPECIFIC IMMUNITY IN PATIENTS WITH COMMON MIGRAINE. Journal of Clinical Laboratory Analysis 4 (1). 19.

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

(30) (Jarisch R. Wantke F. Wine and headache. International Archives of Allergy & Immunology. 110(1):7-12, 1996 May).

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