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Pharmacological Treatment:
Pharmacologic treatment of migraine includes simple analgesics and NSAIDs for acute to moderate migraine attacks (Silberstein 1999, Stewart 2000, Lipton et al 2001). NSAIDs appear to prevent neurologically mediated inflammation in trigeminovascular system through inhibition of prostaglandin synthesis (Dalessio, 1994). Combination therapy with prokinetics such as Metoclopramide and Domperidone increases the absorption of NSAIDs and analgesics and alleviate migraine related nausea and vomiting (Bartleson 1994). Over the counter combinations of acetaminophen, caffeine and aspirin was approved for treating migraine in US due to its efficacy in relieving migraine pain and its associated symptom more than simple analgesics (Fettes 1999, Weitzel, 1999) see in Table No. 3 below.

Table No. 3: (Peter, 2010)

Opiates analgesics:
Narcotic analgesic drugs like oxycodone, butorphanol, meperidine, hydromorphone is effective but generally should be reserved for medications in treating severe infrequent headache in whose conventional therapies are contraindicated or as rescue medications after patients have failed to conventional therapies, opioid therapy should be supervised closely (Weitzel 1999) shown in Table No. 4 below.

Table No. 4: WHO analgesic ladder (Phillips et al, 1998)

Adjunctive antiemetic therapy is useful for combating the nausea and vomiting that accompany migraine headache and medication used to treat acute attacks eg: ergotamine tartrate, dihydroergotamine and ergotamine are useful in treating moderate to severe attacks of migraine (Silberstein 2000). Dihydroergotamine in injectable form is more effective than nasal spray but with more side effects. A single dose of anti-emetics such as metoclopramide, chlorpromazine administered 15-30 minutes before ingestion of oral absorptive migraine medication is often sufficient. Metaclopramide used to reverse gastroparesis and improve absorption from gastro- intestinal tract during severe attacks. Dopamine antagonist drugs have successfully used as monotherapy for treating intractable headache. Drowsiness and dizziness were occasionally reported in migraineurs with the use of dopamine antagonist (Matchar, 2000).

Triptans or serotonin receptor agonists have a significant advance in migraine pharmacotherapy; this class includes sumatriptan, zolmitriptan, naratriptan, etc. Relief of migraine headache results with three key actions i.e., vasoconstriction of intracranial blood vessels, inhibition of vasoactive neuropeptides, interruption of pain signal transmission in trigeminal nuclei through stimulation of 5 HT ID receptors (Ferrari 1998,Hargreaves 1999). The triptans are first line therapy for patients with moderate to severe migraine or rescue therapy when non-specific medications are ineffective, as compared to first generation (sumatriptan), second generation triptan (naratriptan) shows high bioavailability and longer half life (Tfelt et al 2000, Deleu, 2000). First generation triptans (44%) shows more recurrence than second generation triptans (17%) (Mathew et al 2000, Stark 2000). Triptans are contraindicated in patients with history of ischemic heart disease, uncontrolled hypertension, cerebrovascular diseases and they are also contraindicated in patients with hemiplegic and basilar migraine. Concomitant therapy with Selective Serotonin Reuptake Inhibitors (SSRI) should be carefully monitored because of isolated reports of serotonin syndrome in sumatriptan treated patients. This drugs have revolutionized many lives  of severe migraine and  act as powerful option for migraine attack .These are available various dosage forms like sprays, tablets, injections and suppositories ( Goadsby et al. 2002). Sumatriptan is contraindicated in pregnancy and lactation as it is less teratogenic but with high preterm births (Evans, 2008) and even excreted in breast milk (Horton et al. 1996). Almotriptan 12.5 mg has shown to abate migraine attack effectively when given in early phase of attack within 1 hour (Goadsby, 2008).

Prophylactic Treatment:
β - blockers are widely used drugs for migraine prophylaxis with intrinsic sympathomimetic activity are ineffective for migraine prophylaxis. β blockers are used with caution in patients with cardiovascular diseases and asthma. They reduce the brain cell activities which are involved in migraine. These are generally available in tablets and capsules forms (migrainetrust.org).
Amitriptyline is anti-depressant used in migraine prophylaxis it reduces frequency, severity   and duration of migraine attacks (Ramadan, 2000). Other tricyclic anti-depressants have shown beneficial effects in small doses in treating migraine prophylaxis. They acts as antagonist of 5-HT2 receptor or suppresses serotonergic neuronal activity in brain stem (Silberstein 2000, 2002).
Anticonvulsants (valproic acid and divalproex sodium) 1:1 can reduce frequency of headaches by atleast 50% in up to 65% of migraineurs. Its mechanism is unclear in migraine (Silberstein 2002).
Calcium channel blockers, among this class verapamil is a drug of choice for prevention of migraine it is generally considered as second or third-line prophylactic agent with established clinical benefit are ineffective or contraindicated (Silberstein 2000, Goadsby 2000) and flunarizine (sibelium) which is generally prescribed by specialist. These drugs reduce calcium entry into neurons making them less excitable and blocks dopamine receptors in brain. (migrainetrust.org)

New developments in migraine therapy:
Botulinum toxin type A: (onabotulinum toxin A; BTA) It inhibits the release of acetylcholine at motor nerve terminals (Simpson, 1981). This action led to its use in the treatment of movement disorders, such as dystonia, post-stroke spasticity and hyperhidrosis (Jankovic, 2004) and neuropathic pain, lower back pain, myofascial pain, bladder pain (migrainetrust.org). Its cosmetic use suggests the potential benefits in headache. Basic experimental studies showed anti-nociceptive properties in some standard models, such as rats with formalin-induced pain, (Cui et al., 2004) which provided the rationale for its development in headache prevention (Aoki, 2005). According to rami burstein, botulinum toxin inhibits pain in chronic migraine by reducing expression of certain pain pathways involving nerve cells in trigeminovascular system that plays a key role in the headache phase of migraine attack.

Neuromodulation: Neuromodulatory approaches are currently focusing on the stimulation of the Greater Occipital Nerve (GON). The targeted synapses and neurons are located in the trigeminocervical complex and receive convergent input from the GON as well as from the trigeminal nerve (Doare et al, 2006).  The functional imaging studies have shown that central processing of migraine pain signals in the thalamus could be modified by GON stimulation (Matharu et al, 2004). The use of occipital nerve stimulation for the treatment of intractable head pain in human beings was first proposed in 1999, when a series of cases of intractable occipital neuralgia responding to occipital nerve stimulation were reported (Weiner et al, 1999) these device (gamma core) a trans cutaneous vagus nerve stimulator is placed on the sides of neck where the stimulation is increased slowly and muscles contractions are felt under skin. It is held about 90 seconds.
• Pain relief in 20 % of patients within 2 hours of use
• Recovery from disability caused by migraine
• Relief of sickness, photophobia and phonophobia.( migrainetrust.org)


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