**2. Pathophysiology**

Because migraine headache development seems to be complex and multifactorial, its exact pathophysiology is complicated and incompletely understood. Classically, migraine headaches were described as a central nervous system event, but recent publications have stressed the role of peripheral nerves [4, 5]. As the evidence for a peripheral explanation of migraine development continues to increase, so does the evidence for surgical decompression as an effective treatment [6–11].

There are four commonly accepted and experimentally substantiated theories that incorporate both central and peripheral nervous system activity. These include: *periaqueductal gray matter dysfunction, interictal cortical derangement, cortical spreading depression*, and *trigeminal nerve irritation*. The combined effect of these neural derangements is a cycle of nerve irritation, inflammation, and sensory hypersensitivity in the peripheral nerve [12–14]. In migraine headaches, these derangements occur in the areas of trigeminal innervation. A recent microscopic and proteomic analysis indicated that there are indeed biostructural differences in myelin between some peripheral nerves excised from migraine patients and peripheral nerves excised from patients without migraines [15].

One theory that explains the cycle of trigeminal irritation and hypersensitization is the anatomical relationship between peripheral nerves and surrounding musculature. Trigger points for nerve irritation are located at points of intersection between nerve and muscle. One specific example is the interaction between the supratrochlear and supraorbital nerve branches of the ophthalmic division of the trigeminal nerve and the corrugator and depressor supercilii muscle [16]. The observation that many patients with frontal migraines have supercilii hypertrophy supports the theory that muscle impaction on the nerve at least plays a role in inducing migraine pain [17]. Furthermore, the beneficial effect of onabotulinumtoxinA injection into this muscle group reinforces this notion [18, 19]. Other trigger sites of nerve and muscle interaction include the zygomaticotemporal branch of the maxillary division of the trigeminal nerve as it pierces the temporal muscle and the greater occipital nerve (GON) as it passes through the splenius capitus muscle.
