The trigeminal system: The meningovascular complex- A review

Abstract

Supratentorial sensory perception, including pain, is subserved by the trigeminal nerve, in particular, by the branches of its ophthalmic division, which provide an extensive innervation of the dura mater and of the major brain blood vessels. In addition, contrary to previous assumptions, studies on awake patients during surgery have demonstrated that the mechanical stimulation of the pia mater and small cerebral vessels can also produce pain. The trigeminovascular system, located at the interface between the nervous and vascular systems, is therefore perfectly positioned to detect sensory inputs and influence blood flow regulation. Despite the fact that it remains only partially understood, the trigeminovascular system is most probably involved in several pathologies, including very frequent ones such as migraine, or other severe conditions, such as subarachnoid haemorrhage. The incomplete knowledge about the exact roles of the trigeminal system in headache, blood flow regulation, blood barrier permeability and trigemino-cardiac reflex warrants for an increased investigation of the anatomy and physiology of the trigeminal system. This translational review aims at presenting comprehensive information about the dural and brain afferents of the trigeminovascular system, in order to improve the understanding of trigeminal cranial sensory perception and to spark a new field of exploration for headache and other brain diseases.

Keywords: anatomy; brain innervation; cranial sensitivity; dura mater innervation; migraine; trigeminal system; trigemino-cardiac reflex; trigeminovascular system.

FIGURE 1

Skin territory of the three divisions of the trigeminal nerve. The ophthalmic nerve (V₁) supplies the eye bulb including cornea, upper eyelid, back of the nose and skin of the forehead. The maxillary nerve (V₂) innervates the cheek, lover eyelid, lateral part of the nose, upper teeth and gingiva and hard palate. Finally, the mandibular nerve (V₃) supplies the mandibular gums and teeth, skin in the temporal region, part of the auricle and lower lip

FIGURE 2

Dural territory of the three divisions of the trigeminal nerve. (after Penfield & McNaughton, 1940; Lee, Hwang, et al., 2017; Lee, Shin, et al., 2017; Gray's Anatomy, 40th ed., Standring, Intracranial region, p. 433, 2008). The supratentorial dural innervation depends on three main routes: a rostral route(V₁ r), which innervates the anterior cranial fossa and anterior part of the falx, and following the anterior and posterior ethmoidal nerves to connect to the V₁; a caudal route(V ₁c), for the transverse sinus, torcula, tentorium and posterior part of the falx, and which follows the tentorial nerve to reach the V₁; and a lateral route (V₂ and V₃), which innervates the middle cranial fossa and follows the meningeal branches of V₂ and V₃

FIGURE 3

Proposed mechanism of activation of the trigeminovascular in migraine following cortical spreading depression (after Pietrobon & Moskowitz, 2014). During cortical spreading depression (CSD), neurons locally release various proinflammatory signalling molecules (a), which in turn induce glial synthesis of prostaglandins and cytokins (b) (direct pathway). These molecules activate the trigeminal receptors located on the pia and pial arteries, and produce a nervous signal running ortho and antidromically; orthodromically (c), this signal reaches the ganglion of the trigeminal nerve and transmits the nociceptive message to the central nervous system. The CSD‐induced antidromical activation of the trigeminal nerve (d) is supposed to follow the trigeminovascular pathway, especially along the middle meningeal artery and to release vasoactive proinflammatory peptides in the dura mater (indirect pathway). This produces vasodilatation, plasma extravasation and local activation of dural mast cells, the later producing a long‐lasting activation and sensitization of dural nociceptors