Migraine is typically characterised by a recurrent unilateral headache of moderate to severe pain intensity that can be described as ‘throbbing’ in nature (International Headache Society, 2013). Migraine can be accompanied by additional symptoms, such as (International Headache Society, 2013):

  • nausea
  • visual disturbances
  • phonophobia/photophobia

A patient with migraine may experience an attack in stages, with their symptoms evolving over several hours and sometimes lasting days (Lipton et al., 2002; Kelman, 2006; Ng-Mak et al., 2011; Burstein et al., 2015; Charles & Hansen, 2015; American Migraine Foundation, 2018).

Phases of migraine

Figure 9: Phases of migraine.

Prodromal phase

Also denoted as pre-headache or premonitory phase, the prodromal phase is experienced hours or even days before a migraine attack (Burstein et al., 2015; American Migraine Foundation, 2018). Nearly 30–40% of migraine patients experience prodrome with symptoms including (American Migraine Foundation, 2018):

  • repetitive yawning
  • food cravings
  • neck stiffness/pain
  • fatigue

Aura phase

Aura refers to a complex of neurological symptoms. Aura may occur within 1 hour before the onset of migraine headache, or after the headache phase has initiated, and may continue into the headache phase (International Headache Society, 2013). Approximately 30% of patients with migraine experience auras (Lipton et al., 2002) with symptoms occurring in combination or sequentially for 5–60 minutes per symptom (Charles & Hansen, 2015; American Migraine Foundation, 2018).

Table 2: Symptoms associated with the aura phase (Charles & Hansen, 2015; American Migraine Foundation, 2018)

Symptoms associated with the aura phase.


Headache phase

In this phase, pain can range from moderate to severe and lasts from 4 to 72 hours. Effects are not limited to the head and may affect the entire body (American Migraine Foundation, 2018).

Table 3: Characteristics of the headache phase (American Migraine Foundation, 2018)

Characteristics of the headache phase

Postdrome phase

Migraine recovery may take hours to a few days, with approximately 70% of patients experiencing postdrome (Kelman et al., 2006; American Migraine Foundation, 2018).

Sometimes referred to as a post-headache, the postdrome phase may be experienced in migraine even when headache is absent (American Migraine Foundation, 2018). This phase of the migraine attack is commonly termed the “headache hangover,” and is described as the “lingering effect,” or the patient feeling “wiped out” (Ng-Mak et al., 2011). Postdrome symptoms are possibly the result of abnormal cerebral blood flow, which can last 24 hours after the headache stage.

Postdrome symptoms include (Ng-Mak et al. 2011; Burstein et al., 2015; American Migraine Foundation, 2018):

  • altered mood/depression
  • poor concentration and comprehension
  • weakness
  • fatigue or tiredness
  • dizziness
  • nausea

Migraine symptoms and the central nervous system

Migraine symptoms such as pain localisation, photophobia and phonophobia involve the somatosensory, auditory and visual systems of the central nervous system (CNS) (Noseda & Burstein, 2013). Other brain structures implicated in migraine include the hypothalamus, amygdala and insula, which may play a role in migraine-related changes in hormones, emotions and moods (Noseda & Burstein, 2013).

Abnormal signalling in the trigeminal system causes neurogenic inflammation and central sensitisation of signal processing in patients with migraine (Edvinsson et al., 2012).

Central sensitisation causes (Edvinsson et al., 2012; Burstein et al., 2015; de Tommaso & Sciruicchio, 2016):

  • longer lasting pain, as the effects of nociceptive stimuli continue after stimulation has ended
  • more severe pain, because nociceptive stimuli are amplified
  • easily-triggered pain due to a decreased pain signalling threshold
  • pain triggered by stimuli that are normally non-painful

Cortical spreading depression

Migraine aura has been associated with cortical spreading depression (CSD). With CSD, a slowly spreading wave of electrophysiological depolarisation causes prolonged inhibition of cortical activity (~30 min) (Noseda & Burstein, 2013; Ayata & Lauritzen, 2015). The rate of spread correlates with visual aura effects (Hadjikhani et al., 2001; Noseda & Burstein, 2013) and is linked with the subsequent pain phase (Pietrobon & Moskowitz, 2013).

fMRI visualisation of CSD corresponding with aura.

Figure 10: fMRI visualisation of CSD corresponding with aura (Hadjikhani et al., 2001). CSD = cortical spreading depression; fMRI = functional magnetic resonance imaging.

Cortical depolarisation in CSD is associated with the local release of CGRP by perivascular nerves (Noseda & Burstein, 2013). Consequent neurogenic inflammation contributes to sustained activation of the meningeal nociceptors and the TGVS (Noseda & Burstein, 2013; Pietrobon & Moskowitz, 2013; Russo, 2015). Neurogenic inflammation then leads to central sensitisation, hypersensitivity and abnormal signal processing (Ho et al., 2010; Raddant & Russo, 2011).

Cortical depolarisation.

Figure 11: Cortical depolarisation. CSD = cortical spreading depression.

Gastric effects of migraine

Delayed emptying of the stomach (gastroparesis) produces symptoms of nausea and vomiting (Parkman, 2013). Gastroparesis may occur during or between migraine attacks and it has been suggested that imbalances in sympathetic-parasympathetic tone may contribute to its occurrence (Aurora et al., 2006; Aurora et al., 2013). CGRP is involved in regulation of parasympathetic tone, and increased CGRP contributes to gastroparesis (Clark & Gangula, 2015).