Description
Migraine is among the most common
neurological disorders affecting humans,
which is ranked 7th most disabling by the
WHO. The underlying pathophysiology will be
discussed herein; however the readers are also
directed towards recent reviews exploring novel
genetic susceptibility loci and therapeutic
targets.1,2 It is now widely accepted that migraine
is a disease of the brain with the pain component
reliant on activation and disrupted modulation of
the trigeminovascular system (Figure 1).3
The anatomy of the trigeminovascular
system
The trigeminovascular system originates in the
dense plexus of nociceptors which innervate the
cranial vasculature and dura matter, the central
projections of which travel via the trigeminal
ganglion (TG) and synapse on second order
neurons in the dorsal horn giving rise to the trigeminal
cervical complex (TCC). Activation of these
sensory afferents results in the release of a number
of neuropeptides, in both humans and animals,
which have actions on the cerebrovasculature and
spinal cord. The TCC has direct ascending connections
with areas of the brainstem (locus coeruleus
(LC) and periaqueductal grey (PAG)), thalamus
and hypothalamus via the trigeminothalamic and
trigeminohypothalamic tracts en route to cortical
structures. In addition to the ascending projections
there is also a reflex connection from the TCC to
the parasympathetic system via the superior salivatory
nucleus (SuS) and sphenopalantine ganglion
(SPG). This connection results in cranial autonomic
features, which are seen in approximately
30-40% of migraineurs, are diagnostic for cluster
headache and, currently a target of neurostimulation
and proposed action of oxygen,4 and efferent
connections from the facial and cervical
dermatomes (via cervical ganglia, CG).
Migraine is a disorder of dysfunctional
central sensory processing
A combination of seminal preclinical and brain
imaging studies have highlighted the importance
of key pontine, brainstem and diencephalic structures
involved in the pain neuroaxis in migraine.