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Basic Physiology – Pain Sensitive Structures in the Brain

  1. Dura            
  2. V Nerve       
  3. IX Nerve      
  4. X Nerve       
  5. Blood Vessels


  1. It is an episodic headache that is associated with certain features such as sensitivity to light, sound, or movement (formication); nausea and vomiting often accompany the headache.
  2. Patient may have aura (classical migraine) or may not have aura (common migraine)

Associated symptoms include:

  1. Paraesthesia with tingling and numbness
  2. Other focal neurological symptoms such as clumsiness and weakness.

Variants of Migraine

Focal migraine

Is characterized by transient dysphagia, hemisensory symptoms or even focal weakness in addition to other symptoms of migraine

Migraine sine migraine

Is characterized by episodic visual disturbances without headache. Elderly patients with a history of classical migraine are typically affected

Retinal migraine

Is characterized by acute transient unilateral loss of vision. This may occur in middle aged persons without past history of migraine.

Ophthalmoplegic migraine

It is characterized by a recurrent transient third nerve palsy which begins after the headache. (AIPG 2011)

Familial hemiplegic migraine

Is characterized by a failure of full recovery of focal neurological features after an attack of migraine subsides

Basilar migraine

(AIPG 2011)

Occurs in children

It is characterized by a typical migrainous aura associated with numbness and tingling of lips and extremities which is often bilateral

Ataxia of gait and speech also occurs, with occasional impairment of consciousness

Table: Simplified Diagnostic Criteria for Migraine

Repeated attacks of headache lasting 4–72 h in patients with a normal physical examination, no other reasonable cause for the headache, and:

At least 2 of the following features: 

Plus at least 1 of the following features: 

1. Unilateral pain

1. Nausea/vomiting

2. Throbbing pain

2. Photophobia and phonophobia

3. Aggravation by movement


4. Moderate or severe intensity


MIDAS Migraine Disability Assessment Score.


Important Points:
  1. Migraine has its activators, referred to as triggers.
  2. Triggers are: bright lights, sounds, hunger; excess stress; physical exertion; barometric pressure changes; hormonal fluctuations during menses; lack of or excess sleep; and alcohol.

Acute Attack Therapies for Migraine

  1. NSAIDs
  2. 5-HT1 Agonists:
    1. Stimulation of 5-HT 1B/1D receptors can stop an acute migraine attack.
    2. Ergotamine and dihydroergotamine are nonselective receptor agonists.
    3. The triptans are selective 5-HT 1B/1D receptor agonists.
    4. Sumatriptan affect blood flow by decreasing cerebral vasodilatation. Example of triptans (e.g naratriptan, rizatriptan, eletriptan, sumatriptan, zolmitriptan, almotriptan, frovatriptan).
Important Points:

Drug of choice of acute attack of migraine = Sumatriptan

  1. Dopamine antagonists
    Chlorpromazine, prochlorperazine, metoclopramide.
Preventive treatments in migraine (Ref. Hari. 18th ed., Pg-121)
  1. Pizotifen (benzocycloheptene based drug)
  2. Beta blocker: Propranolol
  3. Tricyclic: amitriptyline Dothiepin, Nortriptyline
  4. Anticonvulsants: Topiramate, Valproate, Gabapentin
  5. Serotonergic drugs: Methysergide, Flunarizine

Drugs which are not effective as migraine prophylaxis: Verapamil, Nimodipine, Clonidine, SSRIS, fluoxetine


Recent Advances: (Newer Drug for Migraine) Not given in 18th Edition of Harrison Also !!!
Telcagepant  is for the acute treatment and prevention of migraine

Mechanism of action
  1. The calcitonin gene-related peptide (CGRP) is a strong vasodilator primarily found in nervous tissue.
  2. Vasodilation in the brain is involved in the development of migraine and CGRP levels are increased during migraine attacks.
  3. Telcagepant acts as a  CRLR antagonist and blocks this peptide.
  4. This constrict dilated blood vessels within the brain.


  1. Olcegepant is the first potent and selective non-peptide antagonist of CGRP receptor.
  2. It is an intravenously formulated treatment for acute attacks of migraine.
  3. It attenuates arterial dilation induced by CGRP.

Table 14-8 Clinical Features of the Trigeminal Autonomic Cephalalgias (Ref. Hari. 18th ed., Pg-123)


Cluster Headache

Paroxysmal Hemicrania











Stabbing, boring

Throbbing, boring, stabbing

Burning, stabbing, sharp




Severe to excruciating


Orbit, temple

Orbit, temple


Attack frequency

1/alternate day– 8/d

1–40/d (>5/d for more than half the time)


Duration of attack

15–180 min

2–30 min

5–240 s

Autonomic features



Yes (prominent conjunctival injection and lacrimation) 

Migrainous features




Alcohol trigger




Cutaneous triggers




Indomethacin effectiveness


Abortive treatment

a. Sumatriptan

No effective treatment

Lidocaine (IV)

b. Oxygen inhalation (best treatment)

Prophylactic treatment








Note: SUNCT = Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing

  1. Cluster Headache (Ref. Hari. 18th ed., Pg- 122)
    1. It occurs in middle age (20 – 50 yrs) males
    2. There is severe, throbbing, strictly unilateral headache accompanied by red eye and lacrimation but vision is not affected.
    3. Associated symptoms:
      These are typical and characteristic:
      1. Homolateral lacrimation
      2. Reddening of eye due to conjunctival congestion
      3. Nasal stuffiness          
      4. Ptosis         
      5. Nausea
    4. Headache occurs between 10 PM to 3 AM.
    5. Alcohol consumption is a important predisposing factor.
    6. Periodicity is the hallmark of cluster headache.
    7. For acute attack best treatment is oxygen inhalation. Sumatriptan(Inj. S/C or Nasal spray)  is also effective in acute attack.
    8. For prophylaxis drugs used are:  Valproate, Lithium, Amitriptyline.
    9. Propranolol is not effective as prophylaxis drug.

Extra Edge: Verapamil and lithium are the best prophylactic drug for Cluster headache.



Cluster headache

1. Lateralized , usually frontotemporal may be generalized


2. All age groups are affected


3. Females are affected more than males


4. Family history present


5. Presentation : Pain


a. Often preceded by aura


b. Builds up gradually


c. May lasts for several hours or longer


d. Usually throbbing but may be dull


e. Onset is after awakening & quietened by sleep. 


6. Associated symptoms include:


a. Nausea, vomiting, diarrhea


b. Photophobia and visual disturbance in the form of photopsia and fortification spectra


c. Paraesthesia with tingling and numbness


d. Other focal neurological symptoms such as clumsiness and weakness.

1. Lateralized, periorbital or less commonly temporal


2. All ages above 10 yrs with peak at 30-50 yrs


3.  Male preponderance (90%). Men affected 7-8 times more than females.


4. Hereditary factors usually absent


5. Presentation: Pain (periodic attacks 1-2/day)


a. Excruciating, deep, explosive pain but only rarely pulsatile


b. Reaches crescendo within 5 minutes


c. Begins without warning


d. Lasts for 45 minutes


e. Commonly awakens the patients from sleep.


6. Associated symptoms:

These are typical and characteristic:


a. Homolateral lacrimation


b. Reddening of eye


c. Nasal stuffiness


d. Ptosis


e. Nausea

  1. Hypnic Headache (Ref. Hari. 18th ed., Pg -128)
    1. This headache syndrome typically begins a few hours after sleep onset.
    2. The headaches last from 15 to 30 min and are typically moderately severe and generalized, although they may be unilateral and can be throbbing.
    3. Headaches are bilateral in most, but may be unilateral.
    4. Patients may report falling back to sleep only to be awakened by a further attack a few hours later; up to three repetitions of this pattern occur through the night.
    5. Daytime naps can also precipitate head pain. Most patients are female, and the onset is usually after age 60.
    6. Photophobia or phonophobia and nausea are usually absent.
    7. The major secondary consideration in this headache type is poorly controlled hypertension; 24-h blood pressure monitoring is recommended to detect this treatable condition.

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